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The dietary supplement industry has estimated sales of over 30billionintheUSandover30 billion in the US and over 100 billion globally. Many consumers believe that dietary supplements are safer and possibly more effective than drugs to treat diabetes. The sheer volume of the literature in this space makes compiling them into one review challenging, so much so that primarily narrative reviews currently exist. By applying the interactive database supplied by the Office of Dietary Supplements at the National Institutes of Health, we identified the top 100 ingredients that appeared most often in dietary supplement products. One-hundred different keyword searches using the ingredient name and the word diabetes were performed using a program developed to automatically scrape PubMed. Each search was retained in a separate Excel spreadsheet, which was then reviewed for inclusion or exclusion. The studies that met the inclusion criteria were evaluated for effect of reducing and controlling diabetes. The PubMed scrape resulted in 6217 studies. For each keyword search only the most recent 100 were retained, which refined the total to 1823 studies. Of these 425 met the screening criteria. The ingredients, fiber, selenium and zinc had the most studies associated with improvement in diabetes. Several popular supplement ingredients (phosphorus, pantothenic acid, calcium, magnesium, glutamine, isoleucine, tyrosine, choline, and creatine monohydrate) did not result in any studies meeting our screening criteria. Our study demonstrates how to automate reviews to filter and collapse literature in content areas that have an enormous volume of studies. The aggregated set of studies suggest there is little clinical evidence for the use of dietary supplements to reduce or control diabetes.
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Hannon et al. Nutrition and Diabetes (2020) 10:14
https://doi.org/10.1038/s41387-020-0117-6 Nutrition & Diabetes
REVIEW ARTICLE Open Access
Use and abuse of dietary supplements in persons
with diabetes
Bridget A. Hannon
1
, William D. Faireld
2
, Bryan Adams
3
, Theodore Kyle
4
, Mason Crow
3
and Diana M. Thomas
3
Abstract
The dietary supplement industry has estimated sales of over $30 billion in the US and over $100 billion globally. Many
consumers believe that dietary supplements are safer and possibly more effective than drugs to treat diabetes. The
sheer volume of the literature in this space makes compiling them into one review challenging, so much so that
primarily narrative reviews currently exist. By applying the interactive database supplied by the Ofce of Dietary
Supplements at the National Institutes of Health, we identied the top 100 ingredients that appeared most often in
dietary supplement products. One-hundred different keyword searches using the ingredient name and the word
diabetes were performed using a program developed to automatically scrape PubMed. Each search was retained in a
separate Excel spreadsheet, which was then reviewed for inclusion or exclusion. The studies that met the inclusion
criteria were evaluated for effect of reducing and controlling diabetes. The PubMed scrape resulted in 6217 studies. For
each keyword search only the most recent 100 were retained, which rened the total to 1823 studies. Of these 425
met the screening criteria. The ingredients, ber, selenium and zinc had the most studies associated with
improvement in diabetes. Several popular supplement ingredients (phosphorus, pantothenic acid, calcium,
magnesium, glutamine, isoleucine, tyrosine, choline, and creatine monohydrate) did not result in any studies meeting
our screening criteria. Our study demonstrates how to automate reviews to lter and collapse literature in content
areas that have an enormous volume of studies. The aggregated set of studies suggest there is little clinical evidence
for the use of dietary supplements to reduce or control diabetes.
Introduction
Dietary supplements comprise a vibrant market in the
United States (US) and around the world. Industry esti-
mates suggest that sales of such products for all indica-
tions amount to more than $30 billion in the US
1
, and
estimates for global sales exceed $100 billion
2
. Supple-
ment use remains popular among consumers, despite the
lack of evidence for many popular supplements on the
market. Consumers may use supplements in hopes of
improving or maintaining their health, to correct a dietary
deciency, or more therapeutically for a specic health
condition.
US regulatory oversight for dietary supplements is dis-
tinctly different from the framework for pharmaceuticals
3
.
Makers of a new drug must submit evidence for safety and
efcacy to the US Food and Drug Administration (FDA)
for prior review and approval before it can be used on the
market. The same standard does not apply to dietary
supplements. Dietary supplements, by law, are not
intended to diagnose, treat, prevent, or cure any disease.
Therefore, FDA-approved evidence of safety and efcacy
for supplements is not needed prior to their appearance
on the market. Likewise, there are no regulations
regarding the validity of products claims that can be
made, with the exception that claims cannot state that a
supplement may treat, prevent, or cure a disease
4
. For
example, a supplement maker cannot claim that their
product is intended for diabetes treatment. They can,
however, claim that a product helps to maintain healthy
blood sugar levels, so long as they are not suggesting that
© The Author(s) 2020
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Correspondence: Diana M. Thomas (diana.thomas@westpoint.edu)
1
Division of Nutritional Sciences, University of Illinois at Urbana-Champaign,
Urbana, IL, USA
2
Department of Kinesiology and Community Health, University of Illinois at
Urbana-Champaign, Urbana, IL, USA
Full list of author information is available at the end of the article.
Nutrition and Diabetes
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the product can help a consumer with elevated blood
sugar. In practice, delineating these distinctions can be
very difcult to make for consumers to interpret the
potential consequences of a supplement
5
.
Another difference between dietary supplements and
pharmaceuticals is the regulation of their manufacturing.
Both drugs and supplements must be manufactured
according to good manufacturing practices (GMPs).
However, supplements must meet the different and gen-
erally lower standard for GMPs that applies to drugs
6
. The
stringent requirements for active drug ingredients do not
apply to supplements. Because a new supplement product
is not subject to FDA approval, an FDA manufacturing
inspection is not required, and the FDA does not routi-
nely analyze the content of dietary supplements.
Responsibility for enforcement regarding potentially
deceptive claims about dietary supplements falls princi-
pally to the Federal Trade Commission (FTC). But the
volume of potential violations far exceeds the capacity of
FTC to take enforcement actions
3
. Claims of potential
efcacy of dietary supplements for preventing or con-
trolling diabetes mellitus are common and may easily be
found from sources that consumers might consider to be
authoritative. For instance, Healthline lists 10 supple-
ments to help lower blood sugar
7
.
What is the evidence for supplements as a benet for
patients with diabetes? The American Diabetes Associa-
tion Standards of Medical Care in Diabetes states that
there is insufcient evidence to support a benet from
supplements for patients with diabetes who have no
underlying deciencies. Thus, they are not recommended
for glycemic control
8
. Despite this, there have been several
narrative reviews highlighting the potential benets of
various supplements for diabetes-related outcomes
911
.
However, many of the studies that have been reviewed
may not be of appropriate design or quality to provide
strong evidence for or against supplement use.
Examining reviews of supplements and their benets is
challenging, because searching directly using key words,
such as diabetesand dietary supplementwithin pubmed.
gov or other medically related search engines results in an
unmanageable set of publications that are incomplete and
difcult to organize. In addition, the active ingredients
within a supplement serve as the basis of many studies and
would not be captured in the search results. The objective
of this review was to identify supplement ingredients
commonly used for diabetes management and evaluate the
scientic evidence supporting their use in patients with type
1 (T1D) and type 2 (T2D) diabetes mellitus.
Methods
Dietary supplement ingredient list
The Ofce of Dietary Supplements (ODS) at the
National Institutes of Health developed a searchable
database, the Dietary Supplement Label Database (DSLD)
available at the URL https://dsld.nlm.nih.gov/dsld/
12
. The
database houses information from approximately 76,000
dietary supplement products commercially available in
the US. Within the advanced search, we selected an
option to search by Label Statement or Health Claims
contains. In this we input the key word diabetes. The
ingredient list for the resulting search was downloaded as
a.csv le and retained. Code was written in the statistical
software R (RCore Team (2013)) to count the number of
times the ingredient appeared in a product.
The ingredients were sorted in descending order by the
number of times the ingredient appeared on a product
label. Spurious information that were not specic ingre-
dients, like total calorieswere removed from the list.
From the remainder of the list the top 100 ingredients
based on how often they appeared in products were
retained (see Supplemental Materials).
Web-scraping program developed to search pubmed.gov
We then used the RSelenium
13
package to create a
program in the statistical software package R (RCore
Team (2013)) to automatically collect or scrapeinfor-
mation from listings and abstracts in the PubMed data-
base pertaining to both the ingredients on our ingredient
lists and diabetes research. The program automatically
combined each ingredient in the nal retained database
derived from the ODS website with (ingredient) AND
Diabeteswhen searched on PubMed, e.g. (Potassium)
AND Diabetes.Additional searches were not made for
diabetes comorbidities or T1D versus T2D. The program
then automated the search with these key words using
PubMed built in lters to lter articles that contained an
abstract and gathered pertinent article information from
PubMed for up to the 100 most recent articles. The
information the program scraped included the title,
author, journal, year, URL, DOI, and abstract. Addition-
ally, the program removed any redundant articles that
may have existed on PubMed. The search also allowed for
agging of certain words in the title and abstract. The
following phrases were agged and counted for each
ingredient: cohort, observational, randomized control trial
(RCT), meta-analysis, systematic review, clinical trial,
HbA1c, fasting glucose, and insulin. Results were auto-
matically retained in separate spreadsheets by ingredient
name.
Article screening
Two members of the research team (BAH and WDF)
screened the 100 most recent abstracts from the included
ingredients. The following information was extracted
from every article: was the study conducted in individuals
with diabetes (yes/no), was the study conducted in an
animal model (yes/no), does the study meet inclusion
Hannon et al. Nutrition and Diabetes (2020) 10:14 Page 2 of 12
Nutrition and Diabetes
criteria (yes/no). Inclusion criteria involved a study
examining the role of the individual ingredient on out-
comes related to diabetes (including glucose, insulin,
HbA1c, diabetes-related complications, etc.) in animal or
human subjects. Exclusion criteria involved studies
examining the effects of a multi-nutrient supplement or
co-nutrients, cross-sectional or observational studies,
studies relying on self-reported dietary or supplement
intake, studies that included caloric restriction, or studies
with an outcome not related to diabetes. If an abstract was
found to meet inclusion criteria, the following informa-
tion was extracted: study type (RCT, single-arm trial,
crossover, meta-analysis, narrative review, etc.), outcome,
and whether results support the use of that ingredient for
T1D or T2D. If a study did not meet inclusion criteria, the
reason for exclusion was noted.
Cross checking and discrepancy resolution
After the rst pass of article screening, four members of
the research team (BAH, WDF, DMT, MWC) cross-
checked the initial abstract screen. Data extracted from
this step included conrmation that the study examines
the effect of a supplement on diabetes-related outcomes
in either a human or animal model and if a discrepancy is
present between the original screener and the cross-
checker. If there was a discrepancy identied, notes were
retained on the reason for the discrepancy. Finally, all
discrepancies were reviewed by DMT for validity. Studies
that had been agged as a discrepancy were reviewed and
discarded or retained after cross-checking retainment
criteria.
Evidence grading
Each included study was assigned to one of the fol-
lowing evidence grades: 1: meta-analysis of human RCTs,
2: human or animal RCT, 3: human or animal single arm
trial, 4: narrative review, position statement, or case
report
14
.
Results
The Preferred Reporting Items for Systematic Reviews
and Meta-Analyses (PRISMA) ow chart for article
screening is provided in Fig. 1. There were 2086 ingre-
dients on the ODS website included the word diabetes in
PRISMA 2009 Flow Diagram
Records idenfied through PubMed
web scrape
(
n =6217
)
Screening Included Eligibility Idenficaon
Records aer truncaon of 100
(n =1823)
Records screened in first review
(
n =1823
)
Records excluded
(n =1398)
Arcles assessed in cross-check
(n =425)
Arcles excluded in cross-
check
(
n = 185
)
Studies included in qualitave synthesis
(n = 240)
Fig. 1 PRISMA Flow Diagram. Article screening process depicted in the preferred reporting items for systematic reviews and meta-analyses
(PRISMA) ow chart.
Hannon et al. Nutrition and Diabetes (2020) 10:14 Page 3 of 12
Nutrition and Diabetes
their label statement or claim. From the 100 most com-
mon ingredients, there were 6,217 articles in PubMed
found in the searches from each ingredient and the key-
word diabetes (Table 1). If ingredients had greater than
100 articles, the 100 most recent were included for
screening. From the remaining 1823 abstracts, 425 were
retained for full text screening. Many studies were
excluded at this phase for evaluation of multinutrient
supplements, observational study design, or outcomes not
related to diabetes. After the 425 articles were evaluated
and discrepancies were resolved, 240 studies remained.
Common reasons for exclusion at this stage included the
use of multinutrient supplementation, reliance on self-
report dietary measures, or outcome not related to dia-
betes. The 240 included studies examined over 100 dif-
ferent diabetes-related comorbidities, including outcomes
related to insulin dynamics (secretion, production, resis-
tance, sensitivity, HOMA-IR, and HOMA-B), glucose
metabolism (postprandial, fasting, oral tolerance, two-
hour oral tolerance, glycemic response, and HbA1c), and
hepatic and pancreatic morphology and function (liver
function tests, steatosis, beta cell function, and histology).
Other studies examined outcomes related to oxidative
stress (antioxidant enzyme activity, antioxidant capacity,
endothelial dysfunction, reactive oxidative species for-
mation, glutathione activity, endoplasmic reticulum
stress, etc.) or molecular and microbial changes (expres-
sion of genes such as GLUT4,NFkB,PI3K,mTOR,TNFα,
TGFβ, and VEGF, gut microbial diversity, microbial dys-
biosis, and concentration of lipopolysaccharide binding
protein). Outcomes related to complications of chronic
hyperglycemia (advanced glycation end product forma-
tion, retinopathy, neuropathy, nephropathy, kidney func-
tion, wound healing, vascular function, immune function,
etc.) and comorbidities of diabetes (body composition,
waist circumference, blood lipid concentrations, blood
pressure, bone integrity, C-reactive protein concentra-
tions, incidence of the Metabolic Syndrome, mortality,
etc.) were also explored. A nal ingredient list with
included studies are outlined below and in Table 2.
References for all included studies are available in the
Supplementary Information.
Water-soluble vitamins
Water-soluble vitamins that had relevant studies
included vitamin C
15
, folate/folic acid
6
, vitamin B12
5
,
vitamin B6
4
, biotin
4
, and niacin
3
. Meta-analyses examin-
ing vitamin C supplementation and diabetes-related out-
comes concluded that supplementation may improve
fasting blood glucose but not HbA1c in individuals with
T2D
1517
. Findings from human and animal clinical trials
were mixed. Three meta-analyses of folate or folic acid
supplementation had conicting ndings
1820
. Relevant
studies examining effects of B12 supplementation were
limited to individuals taking Metformin, as this drug can
deplete serum B12 levels. Human studies on both B6 and
biotin were extremely limited, with narrative reviews on
both vitamins concluding a lack of evidence for their
benet among T2D patients
21
. One meta-analysis on
niacin supplementation was found, which concluded an
increased risk of T2D onset following supplementation
22
.
Fat-soluble vitamins
Vitamin E
22
was the only fat-soluble vitamin with
relevant studies. Included meta-analyses displayed no
benet to measurements of glucose or insulin with the
exception of one showing improvements in HbA1C in
individuals with uncontrolled glycemia and low serum
vitamin E at baseline. Human and animal trials displayed
mixed results on fasting glucose, insulin, and markers of
inammation. Results of human clinical trials were not
dose dependent, exhibiting variability regardless of dose.
Minerals
Minerals were the most widely studied category in this
review, accounting for 106 studies. Included minerals
were chromium
23
, potassium
1
, selenium
24
, sodium
7
, and
zinc
25
. Chromium is well studied in relation to diabetes,
and one notable review highlighted the potential asso-
ciation between chromium deciency and hyperglycemia
and impaired glucose tolerance
26
. However, results from
supplementation trials in both humans and animals were
mixed. One study on potassium supplementation was
conducted in individuals with prediabetes and concluded
that potassium supplementation improved fasting blood
glucose despite weight gain, but no signicant effects were
observed for oral glucose tolerance test or insulin
sensitivity.
Selenium accounted for 25 studies with mostly positive
results. The two meta-analyses investigated risk of dia-
betes following supplementation, but concluded no ben-
et
24,27
. Human clinical trials found improvements in
measurements of glucose, insulin, insulin resistance, and
blood lipids, and markers of inammation. Results from
animal trials include improvements in anti-oxidant
enzyme activity, blood glucose, and insulin sensitivity.
However, one review cites the positive correlation
between selenium and diabetic risk as well as its hyper-
glycemic effects in rats
28
.
Evidence on sodium supplementation was unsub-
stantial. No meta-analyses were included, and the only
human clinical trial found an improvement in GLP-1
expression with no improvements on glycemia, insulin, or
anthropometric measurements.
Thirty-six studies on zinc supplementation met inclusion
criteria, and thirty of those reported positive results. Three
meta-analyses found improvements in fasting glucose,
HbA1c, and insulin
2931
.Anotherfoundimprovementsin
Hannon et al. Nutrition and Diabetes (2020) 10:14 Page 4 of 12
Nutrition and Diabetes
Table 1 Top 100 most common ingredients in the Ofce of Dietary Supplements database that list diabeteson their label or health claim.
Ingredient Number of Articles in PubMed Terms extracted from abstracts
Cohort Observational RCT Meta-analysis Systematic review Clinical trial HbA1c Fasting Glucose Insulin
Protein 2067 4 3 7 2 2 6 9 4 39
Total Carbohydrate493 8 5 14 12 8 20 30 11 52
Calcium 397 10 12 6 4 2 6 3 3 11
Dietary ber 351 6 4 3 2 7 10 7 4 27
Vitamin E 244 4 4 4 2 0 9 4 4 29
Vitamin C 199 7 3 6 5 4 8 6 3 21
Chromium 184 4 0 6 5 2 8 11 7 52
Zinc 182 1 3 5 8 8 11 12 5 43
Folic acid 166 9 6 6 5 5 4 6 4 11
Magnesium 147 8 3 11 5 4 8 7 5 30
Sodium 140 2 3 3 2 2 7 3 2 19
Selenium 120 4 7 8 5 2 13 3 4 28
Potassium 91 2 2 2 1 3 4 1 1 18
Vitamin B12 88 8 3 2 0 4 7 1 2 14
Phosphorus 51 3 6 3 1 1 1 2 0 6
Vitamin B6 48 5 2 1 0 0 4 3 1 6
Trans fat 45 2 2 0 0 0 2 1 0 15
L-Tyrosine 44 1 0 1 0 1 0 2 1 25
Taurine 42 0 0 0 0 1 1 0 0 15
L-Leucine 41 1 1 0 1 1 2 0 0 23
L-Glutamine 38 0 0 1 0 0 0 3 1 12
Caffeine 28 5 0 0 0 1 0 1 0 9
Choline Bitartrate 23 0 0 0 0 0 0 0 0 4
Niacin 21 2 1 0 0 0 2 0 1 5
Biotin 17 0 0 1 1 1 3 1 1 9
Beta-Alanine 15 0 0 0 0 0 0 2 1 5
Beta-Alanine 15 0 0 0 0 0 0 2 1 5
L-Isoleucine 5 1 0 0 0 0 0 0 0 2
L-Valine 4 1 0 0 0 0 0 0 0 2
Creatine Monohydrate 3 0 0 0 1 0 1 0 0 0
Strength Matrix2000000000
Pantothenic acid 2 0 1 1 0 1 0 0 0 0
Caffeine Anhydrous 0 0 0 0 0 0 0 0 0 0
Agmatine Sulfate 0 0 0 0 0 0 0 0 0 0
N-Acetyl-L-Tyrosine 0 0 0 0 0 0 0 0 0 0
Creatine Nitrate 0 0 0 0 0 0 0 0 0 0
L-Citrulline Aspartate 0 0 0 0 0 0 0 0 0 0
Vinpocetine 0 0 0 0 0 0 0 0 0 0
Each ingredient was searched in PubMed using the ingredient name and supplement and506 diabetes. The terms listed above were extracted from the abstract and counted above507 using R.
RCT randomized control trial, HbA1C hemoglobin A1C.
Hannon et al. Nutrition and Diabetes (2020) 10:14 Page 5 of 12
Nutrition and Diabetes
Table 2 Summary table containing number of studies in each study grade category (Meta-analyses =Grade 1, RCT =Grade 2, Single Arm or Cross-over =Grade,
narrative review or Case Study =Grade 4), support for diabetes benet and overall description by supplement ingredient.
Nutrient Total
studies
Meta-
analyses
RCT Single
Arm or
cross-
over
Narrative
review or
case study
Do results support the use of this
supplement for diabetes
management? (Yes, No, Mixed)
Brief summary
Human Animal
Water-soluble vitamins
Niacin 3 1 2–– Yes (1); No (2) Meta-analysis of human RCTs concluded that niacin supplementation resulted in
increased onset of T2DM cases; animal studies examined outcomes of oxidative
stress, glucose tolerance, and insulin sensitivity, with mixed results.
Vitamin B6 4 ––31 Yes (2); No (1); Mixed (1) Supplementation may improve diabetic neuropathy, fasting glucose, and
diabetes-related endothelial dysfunction in mice. Narrative review of human
studies concluded no benet.
Biotin 4 ––13 Yes (2); No (1); Mixed (1) In animals, biotin was only effective when combined with exercise. Narrative
review of human trials concluded that high-dose biotin may improve fasting
glucose and glucokinase function.
Folate/
Folic Acid
63 21Yes (2); No (1); Mixed (3) Meta-analyses concluded conicting ndings on folic acid supplementation for
fasting glucose and HOMA-IR. Supplementation did not result in improvements in
HbA1c or homocysteine, but did improve carotid intima media thickness in adults
with MetS and decreased risk of stroke in adults with T2DM when co-administered
with ACE inhibitor.
Vitamin B12
51–– 4 Yes (2); No (3) B12 supplementation may be important in individuals on Metformin, as this drug
reduces serum levels of the vitamin. Experimental evidence does not support
B12 supplementation for diabetes-related outcomes.
Vitamin C 15 5 4 5 1 Yes (6); No (3); Mixed (6) Meta-analyses concluded that supplementation may improve fasting glucose and
diastolic blood pressure, but not HbA1c, in adults with T2DM. Human clinical trials
conclude no benet of supplementation on fasting glucose, blood lipids, or onset
of T2DM, but may improve anxiety symptoms. Findings from animal models
indicate improvements in antioxidant capacity and T lymphocyte function.
Fat-soluble vitamins
Vitamin E 22 5 8 6 1 1 Yes (12); No (8); Mixed (2) Meta-analyses found no effect on markers of glucose or insulin dynamics with the
exception of one displaying improved HbA1C in subjects with uncontrolled
glycemia at baseline and low baseline Vitamin E levels. Improvements from
human clinical trials indicated mixed ndings. A meta-analysis of animal trials
displayed signicant improvements in wound healing.
Hannon et al. Nutrition and Diabetes (2020) 10:14 Page 6 of 12
Nutrition and Diabetes
Table 2 continued
Nutrient Total
studies
Meta-
analyses
RCT Single
Arm or
cross-
over
Narrative
review or
case study
Do results support the use of this
supplement for diabetes
management? (Yes, No, Mixed)
Brief summary
Human Animal
Minerals
Chromium 37 6 7 21 3 Yes (17); No (8); Mixed (12) Meta-analyses display mixed results on glucose control, HbA1C, and TG
concentrations. Human and animal trials found mixed results on HbA1C, insulin,
and oxidative stress. One meta-analysis found that chromium deciency was
associated with impaired glucose tolerance.
Potassium 1 1–– – Yes (1); No (0) Single trial in humans concluded improvements in fasting glucose, but not OGTT
following supplementation, despite weight gain. weight gain
Selenium 25 2 10 7 2 4 Yes (15); No (5); Mixed (5) No improvement in risk of diabetes in meta-analyses. Human clinical trials suggest
improvements in glucose, insulin, insulin resistance, blood lipids, and
inammation. Animal trials display improvements in anti-oxidant enzyme activity,
blood glucose, and insulin sensitivity.
Sodium 7 153 Yes (5); No (0); Mixed (2) In one human trial, GLP-1 was improved but no other measurements related to
diabetes. Animal trials display improvements in glucose control, insulin
measurements, and body weight.
Zinc 36 4 6 14 1 10 Yes (30); No (4); Mixed (2) Meta-analyses concluded improvements in fasting glucose, HbA1c, fasting insulin,
and markers of diabetic kidney injury. Human RCTs found mixed, but mostly
positive, effects of supplementation on reducted progression to diabetes in pre-
diabetes, improvements in fasting glucose, OGTT, insulin resistance, and blood
lipids. Animal trials suggest zincs potential to augment metformin treatment,
other positive effects on glucose control, insulin, and oxidative stress.
Amino acids
Beta-
Alanine
1––1 Yes (1); No (0) May indirectly improve T2DM complications through increases in intramuscular
carnosine concentrations.
Taurine 17 ––12 3 2 Yes (9); No (3); Mixed (6) Human crossover trials found no effect on insulin sensitivity or platelet
aggregation. Animal work indicates potential benet for complications including
diabetic retinopathy and endothelial dysfunction, but mixed results for fasting
glucose, beta cell function, and glucose tolerance. Narrative reviews cite the
potential of taurine yet the lack of clinical trials.
Hannon et al. Nutrition and Diabetes (2020) 10:14 Page 7 of 12
Nutrition and Diabetes
Table 2 continued
Nutrient Total
studies
Meta-
analyses
RCT Single
Arm or
cross-
over
Narrative
review or
case study
Do results support the use of this
supplement for diabetes
management? (Yes, No, Mixed)
Brief summary
Human Animal
L-Leucine 18 1116 Yes (11); No (4); Mixed (3) Only human RCT found no benet on improvements in HbA1C or insulin
sensitivity. Animal studies evidenced improvements in fasting glucose and OGTT,
but mixed effects on insulin resistance. Supplementation did not improve
pancreatic insulin output. Narrative reviews concluded mixed results on glucose
homeostasis.
Other
Caffeine 3 111 Yes (0); No (2); Mixed (1) Human RCT in T1DM patients concluded caffeine may attenuate post-exercise
drop in glycemia, but also may result in late-onset hypoglycemia. Animal study
showed no benet on platelet aggregation or ATP signaling.
Dietary
ber
26 1 6 10 1 8 Yes (18); No (2); Mixed (6) Many different ber sources were tested. Meta-analysis results show
improvements in HbA1C, HOMA-IR, and insulin levels following soluble ber
supplementation. Human RCTs demonstrated benets of soluble ber on
postprandial and fasting glucose, but not intravenous glucose tolerance. Animal
RCTs examined various soluble bers and prebiotics and demonstrated benets in
body weight, hyperglycemia, hyperinsulinemia, and microbial diversity. Several
narrative reviews on prebiotics suggest their benet for microbial diversity, and
improvements in glucose and insulin concentrations.
Protein 4 111 Yes (2); No (1); Mixed (1) Human RCT results in mixed effects on adipokine proles. Animal trials suggest
benets for insulin sensitivity following beta-conglycinin supplementation; but
glucosamine supplementation induced insulin resistance. A narrative review
suggests milk proteins may improve postprandial glucose.
Trans fat 6 1 4 1 1 Yes (2); No (1); Mixed (2) CLA supplementation impaired insulin sensitivity in men with obesity, but
improved insulin secretion in animal studies, despite other mixed results. Trans-
vaccenic acid improved insulin sensitivity in rats.
Totals 240 27 50 103 13 47
ACE angiotensin converting enzyme, ATP adenosine triphosphate, CLA conjugated linoleic acid, GLP-1 glucagon-like peptide 1, HbA1C hemoglobin A1C, HOMA-IR homeostatic model of insulin resistance, MetS Metabolic
Syndrome, OGTT oral glucose tolerance test, RCT randomized control trial, T1DM type 1 diabetes mellitus, T2DM type 2 diabetes mellitus, TG triglycerides.
Hannon et al. Nutrition and Diabetes (2020) 10:14 Page 8 of 12
Nutrition and Diabetes
markers of diabetic kidney injury
29
. Zinc supplementation
in a trial of pre-diabetic individuals reduced progression to
diabetes along with improvements in fasting glucose, oral
glucose tolerance test (OGTT) results, insulin resistance,
and blood lipids. Other included human trials display mixed
results with many showing improvements in similar mar-
kers. One trial in streptozotocin-induced diabetic rats, zinc
displayed the potential to augment metformins improve-
ments on glucose control
32
. Other animal trials show
mostly positive effects of zinc supplementation on glucose
control, insulin, and oxidative stress.
Amino acids
Eighteen studies on leucine, seventeen on taurine, and
one on Beta-Alanine supplementation met inclusion cri-
teria. Only one human RCT was found for leucine sup-
plementation, and concluded no effect on glucose or
insulin sensitivity
33
. Many potential articles were excluded
for examining multiple amino acids in conjunction. Ani-
mal studies in leucine supplementation indicated poten-
tial benets for glycemia (fasting glucose, oral glucose
tolerance) and pancreatic insulin secretion, but no effect
on β-cell development, fasting insulin, or blood lipid
concentrations. Narrative reviews highlighted the role of
leucine as a potential insulin secretagogue to improve
glucose homeostasis, but the mechanism remains
unknown. Three human crossover trials were identied
for taurine supplementation, two of which concluded no
benet on insulin sensitivity or platelet aggregation
34,35
.
The third was conducted in patients with type 1 diabetes,
and showed benets of supplementation for vascular
stiffness
36
. Among the 12 animal RCTs reviewed, there
were promising results for taurine supplementation on
diabetic retinopathy, endothelial dysfunction, insulin
sensitivity, and polydipsia/polyuria. There were mixed
results regarding beta cell function and glycemia. Narra-
tive reviews stated that taurine may be benecial for
diabetes but cite a lack of clinical evidence.
Fiber, macronutrients, and caffeine
Twenty-six studies were reviewed on dietary ber
supplementation. One meta-analysis of human RCTs
found benecial effects of soluble ber supplementation
on HbA1c, fasting glucose, and HOMA-IR
25
. Human
clinical trials conclude positive results following supple-
mentation of a wide range of bers, including insoluble
ber, galacto-oligosaccharides (GOS), chicory inulin, and
beta-glucan. Animal RCTs concluded benecial effects of
soluble ber supplementation (from wheat bran extract,
GOS, barley, and beta-glucan) on outcomes related to
glucose, HbA1c, and microbial diversity). There were
mixed effects of supplementation on insulin sensitivity.
Narrative reviews highlighted the potential benets of
prebiotics on glycemic and microbial outcomes and
soluble ber for glycemic response, insulin concentra-
tions, and body weight.
Additionally, there were six studies on trans-fat sup-
plementation, four on protein supplementation, and three
on caffeine supplementation that met inclusion criteria.
The most common trans-fat supplementation was con-
jugated linoleic acid (CLA), which negatively impacted
insulin sensitivity in prediabetic men, despite having
benecial effects on insulin secretion in animals
23
. Trans-
vaccenic acid also improved insulin sensitivity and
secretion in animals. In humans, protein supplementation
had mixed effects on adipokine concentrations, yet
improved adiponectin and insulin concentrations in ani-
mals. One study found that glucosamine supplementation
induced insulin resistance in animals
37
. A narrative review
cited milk proteins to potentially improve postprandial
glucose, but more work is needed into the effects of iso-
lated milk proteins (whey, casein), rather than within the
dairy matrix, in order for conclusions to be made
38
.
Caffeine supplementation did not signicantly affect pla-
telet aggregation of ATP signaling in animal studies. A
crossover trial investigated the effects of caffeine on post-
exercise glucose concentrations in individuals with T1D,
and found that it may contribute to late-onset hypogly-
cemia and should be used with caution
39
.
Discussion
This scoping review utilized the ODS Researcher
Database and a novel web-scraping program to sum-
marize existing evidence supporting dietary supplement
use for prevention and treatment of diabetes mellitus.
While there were several supplement ingredients that had
a larger volume of studies suggesting support of their use
(e.g. dietary ber, selenium, and zinc), the overall results
were modest with few human RCTs or meta-analyses
(Table 2). In general, we found that most, but not all,
ingredients that are currently included in supplements for
diabetes had very little to no evidence supporting
their use.
Ingredients that had zero articles meeting our inclusion
criteria were phosphorus, pantothenic acid, calcium,
magnesium, glutamine, isoleucine, tyrosine, choline, and
creatine monohydrate. These ingredients are present in a
total of 1763 supplements in the ODS database that make
a health claim related to diabetes, despite limited evi-
dence. The ingredients with the greatest scientic evi-
dence, ber, selenium and zinc, totaled 572 products in
the ODS database. It is evident that there is a need for
greater cohesion between scientic evidence and con-
sumption of dietary supplements.
Many studies were excluded for relying on self-reported
diet or supplement intake and associations with reduc-
tions in diabetes-related secondary symptoms or for
administering treatment as co-supplementation
17
.We
Hannon et al. Nutrition and Diabetes (2020) 10:14 Page 9 of 12
Nutrition and Diabetes
and other teams have shown the unreliability of self-
reported dietary intake, and its use can lead to the pub-
lishing of inaccurate diet-disease relationships
40,41
. In co-
supplementation, it is impossible to isolate individual
effects of one ingredient if it not examined separately. One
common co-supplementation was Vitamin C and Vitamin
E, which have been examined in a meta-analysis for their
effects on HOMA-IR but concluded no benet. In the
case of reporting a reduction of secondary symptoms of
diabetes, such as improved glycemic control, we are
unsure if this was the primary goal of the study. It is
unclear why these secondary symptoms would be repor-
ted without reporting changes in standard measures for
presence of diabetes, such as insulin levels, fasting glu-
cose, and HbA1c. Clearly stated research questions a
statistical statement of the null and alternative hypothesis
and registration with clincialtrials.gov will eliminate these
doubts
42
.
Previous reviews on supplement use for diabetes mel-
litus have concluded mixed results. Twenty-seven meta-
analyses were identied in the current study, assessing
eight different ingredients. Supplementation of vitamin
B6, folate, vitamin C, vitamin E, chromium, and selenium
was found to have mixed or null effects on diabetes-
related outcomes in meta-analyses. Zinc and ber were
the only two ingredients with consistent positive results in
meta-analyses.
There were many notable narrative reviews assessed in
the present study, which largely concluded a potential
benet for a particular supplement yet acknowledged the
lack of clinical evidence to make such claims. We suspect
that the large volume of literature available in the eld is
not conducive to standard systematic reviews.
Despite lack of clinical evidence, consumers will
continue to take dietary supplements for perceived
benet regarding diabetes, thus it is important for
healthcare providers to be knowledgeable about com-
mon supplements and their potential effects. The role
of supplement use for diabetes management, and its
potential interactions with other medical treatment
approaches, have been reviewed from a pharmacy
standpoint and from that of complementary and alter-
native medicine
11
. As supplement use continues to
grow in the US, it is important for healthcare profes-
sionals to understand the evidence behind supplements
and their potential role as part of medical care. Current
supplement use in the US is around 52% of all adults,
but use increases with age and is more common among
womenthanmen
43
. Among individuals with diabetes,
theprevalenceisashighas59%, however this report is
from the 2014 NHANES cohort, and the current pre-
valence may be higher
44
. The most commonly used
supplements in this population were lycopene, vitamin
D, and vitamin B12.
This study had several strengths. The use of R and the
web scrape allowed for thousands of studies indexed in
PubMed to be searched based on inclusion of specic
keywords. This approach also decreases the potential for
human error as it relies on computer extraction of rele-
vant studies rather than manual. Using this method also
allows for a rigorous treatment of the which literature to
include by the applying the capacity to automatically
scrape abstracts. Another strength of this study design is
the broad inclusion criteria. As many included studies
were conducted in animal models, we were able to assess
the effects of supplementation on diabetes-related out-
comes in a preclinical model. This is important, as results
from animal models can still be used as background to
support a dietary supplement claim in conjunction with
results from human studies
45
. Finally, exclusion criteria
involved removing cross-sectional studies or those relying
on self-reported dietary or supplement intake. Self-report
dietary intake has been evidenced to be unreliable due to
reasons such as recall bias, misestimation of portion sizes,
and social desirability bias. To best infer causality between
supplement intake and diabetes-related health outcomes,
the decision was made to only include controlled
experimental trials.
This study is also not without limitations. Included
supplements were limited to those indexed in the ODS
DSLD. This resource is updated regularly and thoroughly
by the ODS and the National Library of Medicine, but it is
still possible that there may be relevant supplements that
were not found in the search strategy. Additionally, terms
related to diabetes (i.e., glycemic control, glucose, insulin,
blood sugar, etc.) or diabetes comorbidities were not
searched. The purpose of this review was to scope the
evidence of current products on the market for diabetes,
and not systematically review all supplements related to
glycemic control and insulin sensitivity. The effects of
individual supplements and diabetes-related outcomes
have been systematically reviewed and meta-analyzed
previously, including chromium
46,47
, magnesium
4850
,
vitamin D
51
, and vitamin E
52
. Finally, the search for arti-
cles was limited to those indexed in PubMed. This
allowed our search to be limited to peer-reviewed articles
that are pertinent to biomedical sciences and could be
searched for pertinent keywords in the title and abstract.
However, the authors acknowledge that there may have
been potentially relevant studies that were not indexed in
PubMed.
In conclusion, there does not exist strong evidence to
support the use of many commercial supplements for
management of diabetes or its comorbidities. Even
existing support is limited due to poor study design and
uncontrolled study methods. Before recommendations
for supplement use to treat diabetes can be made, there
is a need for well-designed human clinical trials to
Hannon et al. Nutrition and Diabetes (2020) 10:14 Page 10 of 12
Nutrition and Diabetes
evaluate the role of these ingredients in diabetes-related
outcomes.
Author details
1
Division of Nutritional Sciences, University of Illinois at Urbana-Champaign,
Urbana, IL, USA.
2
Department of Kinesiology and Community Health, University
of Illinois at Urbana-Champaign, Urbana, IL, USA.
3
Department of Mathematical
Sciences, United States Military Academy, West Point, NY, USA.
4
ConscienHealth, Country Club Dr, Pittsburgh, PA, USA
Conict of interest
The authors declare that they have no conict of interest.
Publishers note
Springer Nature remains neutral with regard to jurisdictional claims in
published maps and institutional afliations.
Supplementary Information accompanies this paper at (https://doi.org/
10.1038/s41387-020-0117-6).
Received: 15 October 2019 Revised: 2 March 2020 Accepted: 5 March 2020
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... Higher zinc intake has been associated with better regulation of fasting glucose, A1C, and insulin levels. Similarly, studies investigating selenium intake, with an RDA of 55 µg/day, highlight improvements in glucose levels, insulin sensitivity, reduction of insulin resistance, decreased blood lipids, and certain inflammatory markers [22,23]. Furthermore, adequate magnesium intake has been linked to better A1C values and improved lipid profiles in individuals with T1D [24,25]. ...
... Also, those achieving target GMI values had significantly higher selenium levels in their diet, which was also shown in recent studies [22,23]. Selenium supplementation may enhance glycemic regulation by reducing reactive oxygen species (ROS) and upregulating the activity of selenoproteins, such as glutathione peroxidases, which are critical in mitigating oxidative damage and improving insulin sensitivity. ...
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Objectives: Dietary supplements have gained attention among people with diabetes as an alternative and complementary treatment, yet there is a limited understanding of supplement use and the motivations behind it. Methods: Data from the National Health and Nutrition Examination Survey (NHANES) from the 2009–2020 period were analyzed, including data on 5784 people with diabetes aged 20 years or older. Dietary supplement use was self-reported. Trends in supplement use were examined across three periods: 2009–2012, 2013–2016, and 2017–2020. Statistical analyses were conducted while considering NHANES’s complex survey design to provide nationally representative estimates for the general noninstitutionalized population of the United States. Results: A total of 61.72% of individuals reported using dietary supplements with a notable increase over time. Supplement users were generally older, more likely to be female, better educated, and had superior blood glucose control with lower smoking rates compared to non-users. Common supplements included multivitamins, multimineral supplements, vitamin D, calcium, zinc, vitamin C, and fish oil. Only 44.58% of individuals used dietary supplements based on medical advice, with the rest opting for self-directed usage. The primary specific health reasons for supplement use were to improve bone health and heart health and enhance the immune system. Conclusions: Dietary supplement use is prevalent among people with diabetes, and most diabetic supplement use is self-directed, which reflects a growing trend toward complementary therapies. Healthcare providers are encouraged to inquire about patients’ use of supplements and offer appropriate guidance as an integral component of comprehensive diabetes management.
... Bên cạnh đó, các loại thực phẩm bảo vệ sức khỏe (TPBVSK) có khả năng hỗ trợ giảm đường huyết cũng được sử dụng để phòng tránh hoặc cải thiện tình trạng sức khỏe của bệnh nhân tiểu đường [3]. Mặc dù các TPBVSK này được giới thiệu có nguồn gốc từ dược liệu tự nhiên và an toàn hơn so với thuốc đặc trị, một số vấn đề liên quan đến sử dụng và lạm dụng các sản phẩm này ở bệnh nhân tiểu đường đã được báo cáo [4]. Một số nghiên cứu về chất hỗ trợ giảm đường huyết (anti-diabetic drugs, ADDs) đã được thực hiện trước đây trên đối tượng là các mẫu TPBVSK với nhiều phương pháp phân tích khác nhau như sắc ký lỏng hiệu năng cao với detector UV-Vis, sắc ký lỏng khối phổ, sắc ký bản mỏng, điện di mao quản, cùng với các phương pháp phân tích quang học và điện hóa [5]. ...
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The mixing of unpermitted drugs with health supplements to increase effectiveness can cause negative effects to consumers, requiring quality testing of these products. In this study, an analytical method for simultaneously determination of 5 anti-diabetic drugs (ADDs) (i.e., metformin, phenformin, buformin, glibenclamide, and gliclazide) in health supplement samples was developed with a combination of ultrasonic extraction, dispersive solid-phase extraction (d-SPE), and liquid chromatography tandem mass spectrometry (LC-MS/MS). Hard capsule, soft capsule, and liquid samples were extracted with methanol twice, followed by activated carbon addition for extract clean-up and LC-MS/MS quantification. The analytical method was validated through various factors such as: specificity, limit of detection, limit of quantification, linearity, repeatability, and recovery. The method had high precision (mean recovery from 88% to 99%, relative standard deviation lower than 10%) and low detection limit of 0.1 mg/kg, meeting the requirements of detection of these substances at trace to ultra-trace levels in complex sample matrices. The validated method was then applied to analyze concentrations of 5 ADDs in 30 health supplement samples. Metformin was detected at a concentration of 2.20 mg/kg in one hard capsule sample, while the remaining samples did not contain ADDs at detectable levels.
... Any further responses from the reviewers can be found at the end of the article 6217 studies suggest limited clinical evidence supporting the use of dietary supplements for reducing or controlling diabetes. 13 At national level, conducting an assessment of knowledge, attitudes, and practices of dietary supplements among patients with Type II diabetes during the current Lebanese economic crisis is crucial for several reasons: 1) access to healthcare services and resources may be limited, leading individuals to seek alternative methods for managing their health conditions. 2) Understanding the knowledge, attitudes, and practices of dietary supplements among patients with Type II diabetes can help healthcare providers identify potential gaps in information and provide targeted education and support. ...
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Background Dietary supplements (DS) use among Lebanese patients with type 2 diabetes mellitus (T2DM) increased widely due to the country’s economic and financial situation. This study was conducted (1) to estimate the prevalence of DS use among persons with T2DM amid the escalating economic crisis in Lebanon; (2) to explore the knowledge, attitude, and practice (KAP) of DS use; and (3) to determine any significant association between socio-economic and socio-demographic factors and the use of DS modality Methods A cross-sectional study was conducted during the worst episode of the economic crisis between October and April 2022 on 460 adult patients with T2DM of both sexes. Patients were interviewed using a pre-tested questionnaire. Results Almost 4 out of 10 patients with T2DM in our study were found to be using DS, where 27.6% take multivitamins frequently. One-third of the participants agreed that nutritional supplements are necessary to control diabetes symptoms and complications. Around 41.1% of the participants complained about hypoglycemia and used DS to control their blood sugar levels (56.4%), while the rest used it to improve their health (35.5%) and control their diet (2.2%). The predictors of DS usage were the patient’s level of education [OR=3.9, CI=1.5-10, p=0.003), self-monitoring of blood sugars (OR=4.9, CI=1.68-14.6; p=0.004) and reading the nutrition label [OR=59.3, CI=6.3-55.8, p=0.000]. Conclusion This study estimated the prevalence of DS use and abuse, among persons with diabetes type II and found three significant predictors of DS use among patients with T2DM. Public health experts should encourage healthy discussions and awareness with their patients to comprehend their views regarding DS use.
... It has been proven that inflammation may cause insulin resistance [12]. The third method is the lipidlowering effect [13]. ...
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Object: The current study aimed to find the correlation between vitamin K2 and chronic diseases such as diabetes and cardiovascular disease by studying a number of physiological and biochemical variables represented by RBS, HbA1c, lipid profile, liver enzymes, as well as antioxidants in men with diabetes and cardiovascular disease in Baghdad. Subject: The study included 80 people whose ages ranged between (15-75) years. Samples were collected from people visiting Al-Imam Al-Kazemin Medical City in Baghdad-Iraq. The experiment was designed into four groups. The first group included 20 healthy people representing the control group. The second group included 20 people with type 1 diabetes (completely dependent on insulin), the third group included 20 people with type 2 diabetes (non-insulin dependent), and the fourth group included 20 people suffering from cardiovascular disease (CVD). Result: The results indicated that there is a relationship between the concentration of vitamin K2 level and the variables that were found in the study, as there was a significant decrease in the concentration of vitamin K2 in all groups of patients compared to the control group, While the levels of only HDL in the lipid profile, as well as GSH, decreased for all groups of patients compared to the control group. Conclusion: conclude from all the results that there is a significant effect of vitamin K2 in improving insulin sensitivity in people with diabetes, thus reducing the risk of diabetes and also important in the prevention and treatment of arterial calcifications and cardiovascular disease.
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The American Diabetes Association (ADA) “Standards of Care in Diabetes” includes the ADA’s current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, an interprofessional expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA’s clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
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Objective: Dietary supplements (DSs) are commonly used supplements among children to support disease treatment, however, overuse and inappropriate prescription of outpatient DS can negatively affect health and treatment costs. This study aimed to evaluate DS use in outpatient treatment in children. Methods: The present study used a cross-sectional descriptive retrospective method based on data from 188,579 outpatient prescriptions of children for 1 year. Results: DSs were commonly prescribed in pediatric patients ≤ 5 years old (63.48%) with diagnosing respiratory, infectious, and gastrointestinal diseases (>50%). DS costs account for a high proportion (24.86%) of total outpatient prescription costs. In addition, pediatric prescriptions containing one DS product (88.16%) showed a higher rate than prescriptions containing two DS products (11.84%) with the main ingredients being vitamin D3 (80.55%), vitamin B6 (63.01%), vitamin B1 (60.22%), and vitamin B2 (59.04%), and calcium (51.0%). The majority of DS products contained multivitamins (69.52%) with DS containing ≥ 5 vitamins of 59.04% and DS containing 2-4 vitamins of 10.48%. Besides, non-compliance with DS prescribing guidelines for age (21.38%), dose (14.13%), and both age and dose (5.54%) was found primarily in highly prescribed DSs (vitamin-amino acid-mineral ingredients), pediatric patients <2 years old, prescriptions containing one DS product or multivitamins, and respiratory disease group (J and R04-09 ICD). The univariate and multivariate regression analyses showed that vitamin-mineral products and groups <2 years old were significantly associated with guideline-adherent DS prescribing for age and/or dose. Meanwhile, foreign DSs and vitamin-mineral ingredients of prescription showed significant associations with guideline-adherent DS prescribing for age or dose. Conclusion: Instructions for DS use regarding recommended age and maximum dosage may not be carefully considered by doctors due to belonging to an over-the-counter medicine group. Therefore, there is a strong need for a national public policy to prevent and control overprescribing and inappropriate prescribing of DS.
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Diabetes mellitus (DM) has emerged as an international health epidemic due to its rapid rise in prevalence. Consequently, scientists and or researchers will continue to find novel, safe, effective, and affordable anti-diabetic medications. The goal of this review is to provide a thorough overview of the role that lifestyle changes play in managing diabetes, as well as the standard medications that are currently being used to treat the condition and the most recent advancements in the development of novel medical treatments that may be used as future interventions for the disease. A literature search was conducted using research databases such as PubMed, Web of Science, Scopus, ScienceDirect, Wiley Online Library, Google Scholar, etc. Data were then abstracted from these publications using words or Phrases like “pathophysiology of diabetes”, “Signe and symptoms of diabetes”, “types of diabetes”, “major risk factors and complication of diabetes”, “diagnosis of diabetes”, “lifestyle modification for diabetes”, “current antidiabetic agents”, and “novel drugs and targets for diabetes management” that were published in English and had a strong scientific foundation. Special emphasis was given to the importance of lifestyle modification, as well as current, novel, and emerging/promising drugs and targets helpful for the management of both T1DM and T2DM.
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Objective To evaluate overall prevalence and trends of use of any supplements, multivitamins/multiminerals (MVMM), individual vitamins, minerals, and non-vitamin, non-mineral (NVNM) supplements among adults with diabetes in the USA. Research design and methods We used a nationally representative sample from the National Health and Nutrition Examination Survey collected between 1999 and 2014. Information on supplement use in the preceding 30 days was collected during interview over 8 continuous 2-year waves. To account for the complex sampling design, weighted analyses were conducted among 6688 US adults with diabetes aged 20–85 years and also stratified by age, sex, race/ethnicity, education, comorbidity status, and diabetes duration. Results Overall, the prevalence of any supplement use (52%–58%; P for trend=0.08) and that of any mineral use (47%–51%; P for trend=0.23) seemed stable over the years studied. Reported use of MVMM slightly decreased from 36% to 32% ( P for trend=0.006). Use of any vitamin products significantly increased from 47% to 52% ( P for trend=0.03). Use of some individual supplements, especially vitamin D, choline, lycopene, and fish oil supplements, significantly increased, while some vitamins, minerals and NVNM supplements decreased over the years. In addition, the trend of any supplement use varied by age, sex, race/ethnicity, or education, but not by diabetes duration or diabetic comorbidities. Conclusions Among US patients with diabetes, use of any dietary supplements or any minerals remained stable, while MVMM use slightly decreased and use of any vitamins increased. Additionally, use of several individual supplements varied significantly over the 16-year period studied.
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Background: Although many studies have shown that low zinc status is associated with diabetes, the putative effects of zinc supplementation on glycemic control are inconclusive. Objectives: The aim of this meta-analysis of randomized controlled trials was to assess the effects of zinc supplementation in preventing and managing diabetes. Methods: PubMed, Embase, and the Cochrane Library were searched for articles that were published through February 10, 2019 and contained estimates for the outcomes of interest. The pooled results were then analyzed with the use of a random-effects model. Results: Thirty-two placebo-controlled interventions were extracted from 36 publications, involving a total of 1700 participants in 14 countries. Overall, compared with their respective control groups, the subjects in the zinc-supplementation group had a statistically significant reduction in fasting glucose [FG, weighted mean difference (WMD): -14.15 mg/dL; 95% CI: -17.36, -10.93 mg/dL], 2-h postprandial glucose (WMD: -36.85 mg/dL; 95% CI: -62.05, -11.65 mg/dL), fasting insulin (WMD: -1.82 mU/L; 95% CI: -3.10, -0.54 mU/L), homeostasis model assessment for insulin resistance (WMD: -0.73; 95% CI: -1.22, -0.24), glycated hemoglobin (WMD: -0.55%; 95% CI: -0.84, -0.27%), and high-sensitivity C-reactive protein (WMD: -1.31 mg/L; 95% CI: -2.05, -0.56 mg/L) concentrations. Moreover, subgroup analyses revealed that the effects of zinc supplementation on FG are significantly influenced by diabetic status and the formulation of the zinc supplement. Conclusions: Our analysis revealed that several key glycemic indicators are significantly reduced by zinc supplementation, particularly the FG in subjects with diabetes and in subjects who received an inorganic zinc supplement. Together, these findings support the notion that zinc supplementation may have clinical potential as an adjunct therapy for preventing or managing diabetes. This trial was registered at PROSPERO as CRD42018111838.
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The present study aims to assess the effects of zinc supplementation on metabolic parameters in patients with type 2 diabetes. A literature search was conducted in PubMedTM, Google ScholarTM, and ScopusTM up to March 2018. Twenty randomized controlled trials met the predefined inclusion criteria and were included in the meta-analysis. Weighted mean difference (WMD) with 95% confidence intervals (CIs) were calculated for net changes in glycemic indices including fasting blood glucose (FBG) and hemoglobin A1c (HbA1c), and in lipid markers including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and high density lipoprotein cholesterol (HDL-c). Subgroup analyses were performed based on intervention and study quality. Compared to controls, zinc supplementation significantly reduced the concentrations of both FBG and HbA1c (FBG WMD: −19.66 mg/dL, 95% CI: −33.71, −5.62; HbA1c WMD: −0.43 mg/dL, 95% CI: −0.80, −0.07). The pooled estimate showed a significant decrease in serum TC and LDL-c, and increase in serum HDL-c levels in treatment group compared with the control group (TC WMD: −18.51 mg/dL, 95% CI: −21.36, −15.66; LDL-c WMD: −4.80 mg/dL, 95% CI: −6.07, −3.53; HDL-c WMD: 1.45 mg/dL, 95% CI: 1.40, 1.51). Subgroup analysis of “no co-supplement” intervention demonstrated significant differences for mean changes in HDL-c and FBG levels, whereas subgroup analysis of high quality studies showed significant differences for mean changes of LDL-c, HDL-c, and FBG levels. Results suggested that zinc supplementation reduces FBG, HbA1c and LDL-c levels and increases HDL-C levels; however, these changes were related to intervention and quality of studies.
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In 2007, supplementation with the trace element selenium in a trial was unexpectedly found to be associated with an excess risk of type 2 diabetes. Given the concerns raised by these findings and the large number of recent studies on this topic, we reviewed the available literature with respect to this possible association. In this paper, we assessed the results of both experimental and nonexperimental epidemiologic studies linking selenium with type 2 diabetes incidence. Through a systematic literature search, we retrieved 50 potentially eligible nonexperimental studies and 5 randomized controlled trials published through June 11, 2018. To elucidate the possible dose–response relation, we selected for further analysis those studies that included multiple exposure levels and serum or plasma levels. We computed a pooled summary risk ratio (RR) of diabetes according to selenium exposure in these studies. We also computed a RR for diabetes incidence following supplementation with 200 µg/day of selenium compared with placebo in trials. In the nonexperimental studies, we found a direct relation between selenium exposure and risk of diabetes, with a clear and roughly linear trend in subjects with higher plasma or serum selenium levels, with RR at 140 µg/L of selenium exposure compared with a referent category of < 45 µg/L equal to 3.6 [95% confidence interval (CI) 1.4–9.4]. A dose–response meta-analysis focusing on studies with direct assessment of dietary selenium intake showed a similar trend. In experimental studies, selenium supplementation increased the risk of diabetes by 11% (RR 1.11, 95% CI 1.01–1.22) compared with the placebo-allocated participants, with a higher RR in women than in men. Overall, results from both nonexperimental and experimental studies indicate that selenium may increase the risk of type 2 diabetes across a wide range of exposure levels. The relative increase in risk is small but of possible public health importance because of the high incidence of diabetes and the ubiquity of selenium exposure.
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One of the major obstacles that males with diabetes may confront is subfertility or infertility. Thus, the present study investigated the effect of co-administration of metformin and zinc (Zn) on the testes of streptozotocin-induced diabetic rats. Male albino rats were randomly divided into 4 groups: control group; untreated diabetic group; diabetic + metformin group, in which diabetic rats were treated orally with metformin (250 mg/kg) once daily for 4 weeks; and diabetic + metformin + Zn group, in which diabetic rats were treated orally with metformin in combination with Zn (10 mg/kg) once daily for 4 weeks. Concomitant administration of metformin and Zn produced a significant decrease in serum levels of glucose and insulin and testicular levels of malondialdehyde and tumor necrosis factor α. Additionally, there was a significant increase in serum levels of Zn, testosterone, and follicle-stimulating hormone, as well as testicular total antioxidant capacity and anti-apoptotic protein Bcl-2, when compared with both the diabetic and metformin-treated diabetic groups. Moreover, co-administration of Zn and metformin significantly improved testicular histopathology, with a significant reduction in percent area of collagen fibers and nuclear factor kappa B (p65) immunoreactivity and a significant increase in seminiferous tubule diameter and connexin 43 immunoreactivity as compared with the diabetic and metformin-treated diabetic groups. In conclusion, the combination of Zn and metformin was an efficacious and safe alternative treatment, as it had superior antihyperglycemic efficacy and provided additional benefits over metformin alone in rats with type 2 diabetes.
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With increasing diabetes prevalence in the US general population, many nutritional supplements are taken as alternative medicine by diabetic patients. However, serial trends or patterns in their dietary supplement use are unknown. Using the nationally representative data from the National Health and Nutrition Examination Survey (NHANES) collected between 1999 and 2014, we evaluated prevalence and trends of use of any supplements, multi-vitamins/multi-minerals (MVMM), individual vitamins, minerals, and non-vitamin, non-mineral supplements. Information on supplement use in the preceding 30 days was collected during the interview over 8 continuous 2-year waves. Analyses were conducted among 6,348 US diabetic adults aged 20 to 85 years (pregnant women excluded) and also stratified by age, race/ethnicity, gender, educational backgrounds, comorbidity status, and comorbidity status. Overall, the prevalence of use of any supplement (52%-59%; P for trend=.09) and that of any mineral (47%-51%; P for trend=.24) seemed stable. Use of MVMM decreased from 36% of reported use in 1999-2000 to 32% in 2013-2014 ( P for trend=.008). Use of any vitamin products increased from 47% to 53% ( P for trend=.04). Use of a few individual supplements including lycopene, vitamin D, and vitamin B12 significantly increased. The trend of supplement use varied by sex and race/ethnicity. In conclusion, among diabetic patients in the United States, use of any dietary supplements or any minerals remained stable, use of MVMM slightly decreased, and use of any vitamins and several individual supplements increased over the past 16 years.
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Globally, diabetes mellitus is not only considered a leading cause of mortality and morbidities but has also created a substantial economic burden. There is growing evidence that foods and their components can be implemented in the prevention and management of type 2 diabetes mellitus (T2DM). Increased dairy consumption has been linked to a lower risk of T2DM. The protective role of dairy foods in the development of T2DM is thought to be largely attributable to dairy nutrients, one of them being dairy protein. There is considerable evidence that milk proteins increase the postprandial insulin response and lower the postprandial blood glucose response in both healthy subjects and patients with T2DM. The exact mechanisms by which milk proteins lower postprandial glucose levels are yet to established; however, the amino acids and bioactive peptides derived from milk proteins are thought to modify a physiological milieu, which includes delayed gastric emptying and the enhancement of incretin and insulin responses, consequently leading to lower postprandial glucose levels. The present review will focus on providing a clear presentation of the potential implementation of milk proteins as a dietary supplement in the prevention and management of T2DM by summarizing the relevant supporting evidence for this particular topic.
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Objective: Evidence from randomized controlled trials (RCTs) suggests that viscous dietary fiber may offer beneficial effects on glycemic control and, thus, an improved cardiovascular disease risk profile. Our purpose was to conduct a systematic review and meta-analysis of RCTs to synthesize the therapeutic effect of viscous fiber supplementation on glycemic control in type 2 diabetes. Research design and methods: MEDLINE, Embase, and Cochrane Central Register of Controlled Trials were searched through 15 June 2018. We included RCTs ≥3 weeks in duration that assessed the effects of viscous fiber on markers of glycemic control in type 2 diabetes. Two independent reviewers extracted data. Data were pooled using the generic inverse variance method and expressed as mean differences (MD) with 95% CIs. Heterogeneity was assessed (Cochran Q statistic) and quantified (I2 statistic). The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to evaluate the overall certainty of the evidence. Results: We identified 28 eligible trial comparisons (n = 1,394). Viscous fiber at a median dose of ∼13.1 g/day significantly reduced HbA1c (MD -0.58% [95% CI -0.88, -0.28]; P = 0.0002), fasting blood glucose (MD -0.82 mmol/L [95% CI -1.32, -0.31]; P = 0.001), and HOMA-insulin resistance (IR) (MD -1.89 [95% CI -3.45, -0.33]; P = 0.02) compared with control and in addition to standard of care. The certainty of evidence was graded moderate for HbA1c, fasting glucose, fasting insulin, and HOMA-IR and low for fructosamine. Conclusions: Viscous fiber supplements improve conventional markers of glycemic control beyond usual care and should be considered in the management of type 2 diabetes.
Article
Glucosamine (GlcN) is a dietary supplement that is widely used to promote joint health. Reports have demonstrated that oral GlcN adversely affects glucose metabolism. Here, we found that oral administration of GlcN induced insulin resistance (IR) and increased plasma glucose levels in mice. Musclin is a muscle-secreted cytokine that participates in the development and aggravation of diabetes. In this study, we found that increased expression of the musclin plays a pathogenic role in GlcN-induced IR in mice. Additional in vivo and in vitro studies showed that 4-PBA inhibited GlcN-induced endoplasmic reticulum (ER) stress and reduced musclin expression, indicating that ER stress might be closely linked to musclin expression. Moreover, the inhibition of musclin gene expression was also observed when sh-RNAs and small molecular compound inhibitors inhibited ER stress-induced PERK and IRE1-associated unfolding protein response (UPR) signaling pathways, and the CRISPR/Cas9 genome editing technology knockout the ATF6-associated UPR pathway in C2C12 myotubes cells. Silencing of the expression of musclin effectively relieved GlcN-affected phosphorylation of Akt, glucose intake and glycogen synthesis. These results suggest that GlcN increased musclin gene expression though UPR, and musclin represents an important mechanism underlying GlcN-induced IR in mice.
Article
Purpose: Observationally, homocysteine is associated with higher risk of diabetes. Folate, which reduces homocysteine, is promising for the prevention and treatment of diabetes. Previous meta-analysis of three trials suggested folate might lower hemoglobin A1c(HbA1c). Methods: An updated systematic review and meta-analysis of placebo-controlled randomized trials was conducted. We searched PubMed using ("folate" or "folic acid") and trial and ("glucose" or "diabetes" or "insulin" or "hemoglobin A1c" or "HbA1c") in any field until February 3, 2017. We also conducted a bibliographic search of selected studies and relevant reviews. Relative risk of diabetes and mean differences in indicators of glucose metabolism between folate and placebo were summarized in a meta-analysis using inverse variance weighting with random effects. Heterogeneity, publication bias, and risk of bias were also assessed. Results: Eighteen trials of 21,081 people with/without diabetes were identified. Folate decreased fasting glucose (-0.15 mmol/L, 95% confidence interval [CI] -0.29 to -0.01), homeostatic model assessment-insulin resistance (-0.83, 95% CI -1.31 to -0.34), and insulin (-1.94 μIU/mL, 95% CI -3.28 to -0.61) but had no clear effect on diabetes or HbA1c. Conclusions: Our study suggests a potential benefit of folate on insulin resistance and glycemic control; the latter requires examination in more high-quality trials.