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Indian Journal of Endocrinology and Metabolism / Jan-Feb 2014 / Vol 18 | Issue 1 1
Hypoglycemia is a not so infrequent condition encountered
in endocrine practice. Considered an inevitable
(though modi able) part of diabetes therapy, hypoglycemia
occurs fairly often, in both type 1 and type 2 diabetes, in
patients on oral hypoglycemic agents and insulin, and in
indoor as well as outdoor settings.[1] As the prevalence
of diabetes rises, and as we try to control glycemia
more aggressively, using the multiple permutations and
combinations of antidiabetic drugs available to us, the
incidence of hypoglycemia is certain to rise. Apart from
this, hypoglycemia is sometimes spontaneous, and may
occur without relation to antidiabetic therapy.
Hypoglycemia is basically a mismatch between
insulin (whether exogenous or endogenous) and glycemic
levels (whether produced by meals or parenteral nutrition).
The excessive insulin levels may be due to excessive dosage,
increased bioavailability, or enhanced insulin sensitivity.
The inappropriate increase in insulin levels leads to a fall
in blood glucose levels, which in turn stimulates a series of
physiological protective mechanisms. These include a release
of glucagon, adrenaline, cortisol, and growth hormone;
among others.[1] These physiological responses are linked with
symptoms, which can be classi ed as adrenergic or autonomic,
neuroglycopenic, and general (usually glucagon-induced).
Hypoglycemia prevention now occupies center stage in
diabetes praxis, as focus moves from a purely ef cacy
oriented approach to one which aims for safety and
tolerability, along with glycemic control. This shift has
occurred in parallel with our understanding of the multiple
deleterious effects of hypoglycemia on various organ
systems; including the heart, brain, and retina.[2]
Hypothyroidism is one of the most common
endocrinopathies worldwide, and its incidence is increasing
rapidly.[3] It is frequently found to coexist with both type 1
and type 2 diabetes mellitus.[4,5] Cross-talk between thyroid
and diabetes has been the topic of many reviews, which
discuss the potential of hyperthyroidism to exacerbate
diabetes,[6] and of antidiabetic therapy (metformin)
to improve thyroid function.[7] The potential role of
hypothyroidism in precipitating hypoglycemia has not
been highlighted adequately in current literature. This
brief communication aims to discuss the link between
hypothyroidism and hypoglycemia, and suggest simple
caveats for clinical practice.
Interest in the hypoglycemic effect of hypothyroidism
began a century ago, even before insulin was discovered.[8]
Hypothyroidism was, by then, a well-known and well-studied
entity, and had been differentiated from hypopituitarism.
The hypoglycemia of hypothyroidism, dyspituitarism,
and Addison’s disease was known to be common
knowledge.[9] Later, literature clearly highlights the importance
of hypothyroidism as a precipitating factor for hypoglycemia,
while reporting prolonged hypoglycemia due to exogenously
administered insulin in hypothyroid patients.[10]
The correlation between diabetes and hyperthyroidism had
also been reported before the advent of the insulin era.[11] In
fact, in his 1947 Nobel lecture, Nobel laureate BA Houssay
clearly mentions thyroid as one of the ‘blood sugar raising’
glands (aneterohypophysis, adrenals, thyroid, etc.)[12]
Recent literature, however, is con icting and confusing.
Some diabetology textbooks choose not to mention
The hypoglycemic side of hypothyroidism
Sanjay Kalra, Ambika Gopalakrishnan Unnikrishnan1, Rakesh Sahay2
Departments of Endocrinology, Bharti Hospital and BRIDE, Karnal, Haryana, 1Chellaram Institute of Diabetes, Pune, Maharashtra,
2Osmania Medical College, Hyderabad, Andhra Pradesh, India
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Corresponding Author: Dr. Sanjay Kalra, Bharti Hospital and BRIDE, Karnal, Haryana, E-mail:
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Kalra, et al.: Hypothyroidism and hypoglycemia
Indian Journal of Endocrinology and Metabolism / Jan-Feb 2014 / Vol 18 | Issue 1
hypothyroidism as a possible factor in the pathogenesis of
hypoglycemia, though they do describe Addison’s disease
and panhypopituitarism.[1] Major thyroidology textbooks do
not mention susceptibility to hypoglycemia as a complication
of hypothyroidism.[13] Other modern reviewers, on the
other hand, clearly emphasize hypothyroidism as one of
the endocrine de ciencies responsible for hypoglycemia.[14]
Yet others refute this concept, proposing the theory that
if hypothyroidism is accompanied by hypoglycemia, it is
in fact a manifestation of panhypopituitarism, rather than
primary hypothyroid disease.[15] Yet others tend to trivialize
the issue (‘although seldom happening, hypothyroid patients
can experience hypoglycemia’).[16]
Yet, case reports have been published which describe the
correlation between hypothyroidism and hypoglycemia,
both in infants[17] and in adults.[18] Robust evidence is also
available which implicates uncontrolled hyperthyroidism
as a cause of poor glycemic control.[19]
Is there a physiologic basis to connect hypothyroidism
and hypoglycemia? And if we go a step further, can
hypothyroidism be postulated as a precipitating factor for
hypoglycemia unawareness?
Hypothyroidism is linked with various hormonal
biochemical and nervous system abnormalities, which
may contribute to hypoglycemia.
The condition is linked with low growth hormone and
cortisol responses to insulin induced hypoglycemia, and
this prevents adequate counter regulatory protection.[20,21] It
must be noted that in some cases, pituitary dysfunction may
be a consequence of primary hypothyroidism, rather than a
cause of thyroid dysfunction. For example, hypothyroidism
reduces basal and stimulated growth hormone levels, by
acting on both the hypothalamus and pituitary.[21] As it
is linked with suboptimal growth hormone response,
the recovery from hypoglycemia may be prolonged in
Hypothyroid patients have relative adrenal insuf ciency,
even if they are not associated with primary adrenal failure.
There is a blunted hypothalamo-pituitary-adrenal response
to hypoglycemia in hypothyroid persons.[22] The reduced
cortisol responses to insulin-induced hypoglycemia that
are noted in hypothyroidism also worsen hypoglycemia.
The role of gluconeogenesis is reduced in hypothyroidism,
both in skeletal muscle and in adipose tissue.[23]
Glycogenolysis is also impaired in hypothyroidism.[24] These
biochemical defects lead to a delayed recovery from
Other abnormalities in hypothyroidism include a
reduction in glucagon secretion,[25] reduced effect of
glucagon on hepatocytes,[26] and slowing of insulin
clearance.[10] Contributory factors also include the effect
of hypothyroidism on the gastro intestinal system. It slows
gastric emptying[27] and decreases intestinal absorption of
glucose as well as portal venous ow.
Modern researchers, on the other hand, have reported
the link between subclinical and overt hypothyroidism on
one hand, and insulin resistance on the other.[28] Reviewers
explain this paradox by contrasting the insulin agonist actions
of thyroid hormones, evident in peripheral tissues, with
insulin antagonist activity in the liver.[16] The hepatic effects
of thyroxin are mediated directly, as well as through the
hypothalamus. Variable effects at peripheral and hepatic levels
may explain discordant results obtained by different workers.
The wisdom collated by the pioneers of endocrinology
seems to have been lost in modern textbooks. This
omission deprives the student of endocrinology of an
important clinical practice pearl, viz.: The hypoglycemic
side of hypothyroidism. This editorial has tried to highlight
a supposedly insigni cant aspect of hypothyroidism, which
has a signi cant impact on contemporary diabetology
practice. Perhaps the reason for this lack of attention is a
lack of clarity regarding the difference between spontaneous
hypoglycemia (as seen in panhypopituitarism) and the
increased predisposition to hypoglycemia encountered in
persons on treatment for diabetes.
The glucoregulatory effects of thyroid hormones carry
great clinical signi cance. Persons with diabetes who
report with a sudden increase in frequency or severity of
hypoglycemic episodes, not explained by changes in diet,
physical activity, or dosage of glucose-lowering drugs, must
be evaluated for hypothyroidism.
The symptoms of hypoglycemia may be nonspeci c, and
may represent subtle neuroglycopenia. A high index of
suspicion must be kept in hypothyroid patients on diabetes
treatment, as the symptoms of counter regulatory hormone
release may be blunted, and there may be an underlying
neurocognitive defect in grossly hypothyroid persons.
The clinical implications of the hypoglycemia-prone features
of hypothyroidism should be taken into account while
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Kalra, et al.: Hypothyroidism and hypoglycemia
Indian Journal of Endocrinology and Metabolism / Jan-Feb 2014 / Vol 18 | Issue 1 3
planning antidiabetic therapy. Person with uncontrolled
hypothyroidism should be given relatively lower doses of
insulin and insulin secretagogues (sulfonylureas). Safer
insulin analogues which are linked with a lower incidence
of hypoglycemia should be preferred.
In patients on treatment for both thyroid disorders and
diabetes, thyroid status should be kept in mind while titrating
antidiabetic therapy. Those with an improving thyroid
status, or falling serum thyroid stimulating hormone (TSH),
may require an increase in dosage of antidiabetic medicines.
Similarly, those with worsening hypothyroidism will need a
reduction in dosage. This down titration will be needed in
patients of Graves’ disease who respond rapidly to therapy.
The TSH lowering or potential thyroprotective effect of
metformin[7] should be considered while assessing thyroid
function reports. Above all, one must follow a panglandular
approach while managing any endocrine illness, and not
neglect the mature wisdom of clinical endocrinology.
1. Heller SR. Hypoglycemia and diabetes. In: Pickup JC, Williams G,
editors. Textbook of Diabetes. Malden: Blackwell; 2003. p. 33.1-33.19.
2. Kalra S, Deepak MC, Narang P, Singh V, Uvaraj MG, Agrawal N.
Usage pattern, glycemic improvement, hypoglycemia, and body
mass index changes with sulfonylureas in real-life clinical practice:
Results from OBSTACLE Hypoglycemia Study. Diabetes Technol
Ther 2013;15:129-35.
3. Unnikrishnan AG, Menon UV. Thyroid disorders in India: An
epidemiological perspective. Indian J Endocrinol Metab 2011;15:S78-81.
4. Kalra S, Kalra B, Chatley G. Prevalence of hypothyroidism in
pediatric type 1 diabetes mellitus in Haryana, Northern India.
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5. Demitrost L, Ranabir S. Thyroid dysfunction in type 2 diabetes
mellitus: A retrospective study. Indian J Endocrinol Metab
6. John HJ. Association of hyperthyroidism with diabetes. Ann Surg
7. Kalra S, Dhamija P, Unnikrishnan AG. Metformin and the thyroid:
An unexplored therapeutic option. Thyroid Res Pract 2012;9:75-7.
8. Janney NW, Isaacson VI. I. The blood sugar in thyroid and other
endocrine diseases: The significance of hypoglycemia and the
delayed blood sugar curve. Arch Intern Med 1918;22:160.
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10. Shah JH, Motto GS, Papagiannes E, Williams GA. Insulin
Metabolism in hypothyroidism. Diabetes 1975;24:922-5.
11. Rohdenburg GL. Thyroid diabetes. Endocrinology 1920;4:63.
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[Last accessed on 2013 May 30].
13. Mc De rmott MT. Overview of the clinical manifestations of
hypothyroidism. In: Braverman LE, Cooper DS, editors. Werner
and Ingbar’s The Thyroid. A Fundamental and Clinical Text. 10th ed.
New Delhi, Philadelphia: Lippincott. William and Wilkins; 2013.
14. Samaan NA. Hypoglycemia secondary to endocrine deficiencies.
Endocrinol Metab Clin North Am 1989;18:145-54.
15. Saleh M, Grunberger G. Hypoglycemia: An excuse for poor glycemic
control? Clin Diabetes 2001;19:161-7.
16. Brenta G. Why can insulin resistance be a natural consequence of
thyroid dysfunction? J Thyroid Res 2011;1:2011.
17. Kurtoglu S, Tutuş A, Aydin K, Genç E, Çaksen H. Persistent neonatal
hypoglycemia: An unusual finding of congenital hypothyroidism.
J Pediatr Endocrinol Metab 1998;11:277-9.
18. Shibutani Y, Yokota T. A case of acetohexamide-induced
hypoglycemia: The influence of hypothyroidism on the metabolism
of acetohexamide. Nihon Naibunpi Gakkai Zasshi 1991;67:42-9.
19. Wu P. Thyroid disease and diabetes. Clin Diabetes 2000;18:38-9.
20. Ridgway EC, McCammon JA, Benotti J, Maloof F. Acute metabolic
responses in myxedema to large doses of intravenous L-thyroxine.
Ann Intern Med 1972;77:549-55.
21. Katz HP, Youlton R, Kaplan SL, Grumbach MM. Growth and
growth hormone. 3. Growth hormone release in children with
primary hypothyroidism and thyrotoxicosis J Clin Endocrinol Metab
22. Kamilaris TC, DeBold CR, Pavlou SN, Island DP, Hoursanidis A,
Orth DN. Effect of altered thyroid hormone levels on
hypothalamic-pituitary-adrenal function J Clin Endocrinol Metab
23. McCulloch AJ, Johnston DG, Baylis PH, Kendall-Taylor P,
Clark F, Young ET, et al. Evidence that thyroid hormones regulate
gluconeogenesis from glycerol in man. Clin Endocrinol (Oxf)
24. McDaniel HG, Pittman CS, Oh SJ, DiMauro S. Carbohydrate
metabolism in hypothyroid myopathy. Metabolism 1977;26:867-73.
25. Clausen N, Lins PE, Adamson U, Hamberger B, Efendić S.
Counterregulation of insulin-induced hypoglycaemia in primary
hypothyroidism. Acta Endocrinol (Copenh) 1986;111:516-21.
26. Müller MJ, Seitz HJ. Interrelation between thyroid state and the
effect of glucagon on gluconeogenesis in perfused rat livers. Biochem
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27. Holdsworth CD, Besser GM. Influence of gastric emptying-rate
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Cite this article as: Kalra S, Unnikrishnan AG, Sahay R. The hypoglycemic
side of hypothyroidism. Indian J Endocr Metab 2014;18:1-3.
Source of Support: Nil, Con ict of Interest: None declared.
[Downloaded free from on Wednesday, September 28, 2016, IP:]
... It is thought to be the precipitating factor for hypoglycemia in diabetic patients. 3 In addition the incidence of hypothyroidism increases with age and is more common in women. 4 The prevalence of T2DM (about 90%) is greater compared to that of T1DM (about 10%) among the diabetes mellitus population due to increase in sedentary lifestyle and obesity. ...
... Our findings showed significantly lowered levels of glucose in diabetic patients with hypothyroidism, as compared to those diabetic patients without hypothyroidism as reported by several studies. 2, 3 These results indicate hypoglycemia in T2DM patients under the influence of hypothyroidism. ...
... Such regulation of drug doses should also be taken into account in the treatment of Graves' disease. After introduction of thyrostatics, when the body's response to treatment is fast, doses of hypoglycaemic agents should be quickly lowered [47]. ...
... Dawki leków hipoglikemizujących, szczególnie pochodnych sulfonylomocznika i insuliny, powinny być odpowiednio mniejsze, a dawkowanie modyfikowane w zależności od wyrównywania hormonów tarczycy [przy zmniejszaniu się stężenia tyreotropiny (TSH) większe dawki leków hipoglikemizujących]. Taka regulacja dawek leków powinna również być brana pod uwagę w przypadku leczenia choroby Gravesa-Basedowa. Po włączeniu tyreostatyków, gdy odpowiedź organizmu na leczenie jest szybka, dawki leków hipoglikemizujących powinny być szybko obniżane [47]. ...
Hypoglycemia is a decrease in blood glucose concentration below the physiological level. It occurs in healthy people and in people with various diseases with inadequate secretion of insulin by β cells, or deficiency of counterregulatory hormones secreted at the moment of hypoglycemia. Hypoglycemia is also associated with diabetes therapy, regardless of whether behavioral therapy, oral hypoglycemic agents, or insulin are used. Distinguishing the causes of hypoglycemia is the basis for taking appropriate therapeutic actions that protect patients against subsequent episodes of lowering blood glucose and complications caused by hypoglycemia.
... Hypothyroidism is associated with various hormonal biochemical and nervous system abnormalities, which can lead to hypoglycemia, such as reduced basal and stimulated growth hormone or cortisol levels, blunted hypothalamo-pituitary-adrenal response, reduced glucogenesis, impaired glycogenolysis, reduced glucagon secretion, and slowing of insulin clearance. [6][7][8] There are well F I G U R E 1 Cutaneous fibromas on the back. ...
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Key Clinical Message Hypoglycemia in non‐diabetic patients is rare and may be due to various etiologies. It is important to recognize hypoglycemia early and appropriately manage hypoglycemia in patients with neurofibromatosis 1 and hypothyroidism. Abstract Non‐diabetic hypoglycemia is not common and can be seen in certain conditions like Neurofibromatosis type 1 (NF1). We report a rare case of 66‐year‐old man with hypothyroidism and NF1 who developed a persistent level 1 hypoglycemia.
... [25] Hypothyroidism, on the one hand, slows down the metabolic rate and on the other hand, is associated with insulin sensitivity, both of these factors can contribute to hypoglycemia. [26,27] Dose adjustment for insulin is needed when a diabetic patient concomitantly suffers from both endocrinopathies. ...
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Introduction: Diabetes and thyroid disorders are the two most common disorders amongst endocrine diseases. Uncontrolled diabetes mellitus (DM) may disturb thyroid metabolism by disturbing the levels of thyroid hormones in the plasma. This study was undertaken to determine the prevalence and thyroid dysfunction in type 2 diabetic population presenting in a public sector tertiary care teaching hospital. Materials and methods: This descriptive cross-sectional study was conducted in Civil Hospital Karachi (CHK) in the department of medicine from October 01, 2018, to March 31, 2019. The study population consisted of 317 patients diagnosed with DM type 2 based on American Diabetes Association (ADA) criteria. Patients with fasting blood sugar ≥ 126 mg/dL, or HbA1c >6.5 (%), and 2 h postprandial blood glucose levels >200 mg/dL were included. After a minimum of 8 h of fasting, plasma samples of patients were collected and sent for fasting blood glucose, HbA1c, FT3, FT4, and thyroid-stimulating hormone (TSH). Descriptive statistics were calculated. Post-stratification Chi-squared test was applied, and a P value of ≤ 0.05 was considered significant. Results: Among all enrolled DM type 2 patients, 207 (65.3%) were male with a mean age of 46.54 ± 8.72 years. Mean fasting blood sugar (FBS), random blood sugar (RBS), and HbA1c were 212.76 ± 26.91 (mg/dL), 328.89 ± 52.89 (mg/dL), and 9.43 ± 2.47 (%), respectively. The mean duration of DM was 7.81 ± 3.15 years. Mean FT3, FT4, and TSH were 113.13 ± 44.40 (ng/dL), 7.63 ± 3.11 (mg/dL) and 2.64 ± 2.57 (mIU/mL), respectively. In the present study, 55 (17.4%) patients had subclinical hypothyroidism, 27 (8.5%) had hypothyroidism, 19 (6.0%) had hyperthyroidism, and 16 (5.0%) had subclinical hyperthyroidism. Significant association of thyroid dysfunction was established with age group, female gender, and family history of thyroid dysfunction (P =< 0.001). Conclusion: The prevalence of thyroid dysfunction is higher among patients with type 2 diabetes mellitus (T2DM), in which hypothyroidism was the most common dysfunction with more prevalence among female patients.
... Importantly, hypothyroidism, both overt and subclinical disease, was also associated with a deterioration of glucose metabolism and elevated whole-body IR; moreover, it appeared to be subject to an increased risk of hypoglycemia as a consequence of the mismatch between insulin and glycemic levels [115,116]. Furthermore, insulin-stimulated glucose transport was reported to decrease in patients with hypothyroidism due to disrupted translocation of GLUT4 on the plasma membrane [117]. On the other hand, IR was correlated with a higher prevalence and larger size of thyroid nodules and increased thyroid volume [118,119]. ...
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Type 2 diabetes (T2D) is considered one of the largest global public-health concerns, affecting approximately more than 400 million individuals worldwide. The pathogenesis of T2D is very complex and, among the modifiable risk factors, selenium (Se) has recently emerged as a determinant of T2D pathogenesis and progression. Selenium is considered an essential element with antioxidant properties, and is incorporated into the selenoproteins involved in the antioxidant response. Furthermore, deiodinases, the enzymes responsible for homeostasis and for controlling the activity of thyroid hormones (THs), contain Se. Given the crucial action of oxidative stress in the onset of insulin resistance (IR) and T2D, and the close connection between THs and glucose metabolism , Se may be involved in these fundamental relationships; it may cover a dual role, both as a protective factor and as a risk factor of T2D, depending on its basal plasma concentration and the individual's diet intake. In this review we discuss the current evidence (from experimental, observational and randomized clinical studies) on how Se is associated with the occurrence of T2D and its influence on the relationship between thyroid pathophysiology, IR and T2D.
... Both hyperthyroidism and hypothyroidism have been associated with complications in insulin signaling, glucose intolerance, and metabolic diseases such as T2D, but the interactions between THs, hyperglycemia, and insulin resistance remain elusive (4,5,41). Moreover, the consequences of hyperthyroidism have been described in more detail than those of hypothyroidism where observations are often quite divergent (3,42). We used Dio2KO zebrafish to investigate the link between THs and glucose homeostasis in more detail in male 16-hourfasted animals. ...
Thyroid hormones (THs) are crucial regulators of glucose metabolism and insulin sensitivity. Moreover, inactivating mutations in type 2 deiodinase (DIO2), the major TH-activating enzyme, have been associated with type 2 diabetes mellitus (T2D) in both humans and mice. We studied the link between Dio2 deficiency and glucose homeostasis in fasted males of two different Dio2-knockout (KO) zebrafish lines. Young adult Dio2KO zebrafish (6-9 months (M)) were hyperglycemic. Both insulin and glucagon expression were increased, while β and α cell numbers in the main pancreatic islet were similar to wild-types. Insulin receptor expression in skeletal muscle was decreased at 6M, accompanied by a strong downregulation of hexokinase and pyruvate kinase expression. Blood glucose levels in Dio2KO zebrafish however normalized around 1 year of age. Older mutants (18-24M) were normoglycemic and increased insulin and glucagon expression was accompanied by a prominent increase in pancreatic islet size and β and α cell numbers. Older Dio2KO zebrafish also showed strongly decreased expression of glucagon receptors in the gastrointestinal system as well as decreased expression of glucose transporters GLUT2 and GLUT12, glucose-6-phosphatase and glycogen synthase 2. This study shows that Dio2KO zebrafish suffer from a transient hyperglycemia, which is counteracted with increasing age by a prominent hyperplasia of the endocrine pancreas together with decreases in hepatic glucagon sensitivity and intestinal glucose uptake. Further research on the mechanisms allowing compensation in older Dio2KO zebrafish may help to identify new therapeutic targets for (TH deficiency related) hyperglycemia.
... The difference between spontaneous hypoglycemia and the increased predisposition to hypoglycemia in patients treated for diabetes is unclear. Persons with diabetes who have a sudden increase in frequency or severity of hypoglycemic episodes, not explained by changes in diet, physical activity, or dosage of glucose-lowering drugs, must be evaluated for hypothyroidism [81]. ...
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Diabetes mellitus is a chronic disease requiring lifelong control with hypoglycemic agents that must demonstrate excellent efficacy and safety profiles. In patients taking glucose-lowering drugs, hypoglycemia is a common cause of death associated with arrhythmias, increased thrombus formation, and specific effects of catecholamines due to sympathoadrenal activation. Focus is now shifting from merely glycemic control to multifactorial approach. In the context of individual drugs and classes, this article reviews interdisciplinary strategies evaluating metabolic effects of drugs for treatment of chronic heart failure (CHF) which can mask characteristic hypoglycemia symptoms. Hypoglycemia unawareness and cardiac autonomic neuropathy are discussed. Data suggesting that hypoglycemia modulates immune response are reviewed. The potential role of gut microbiota in improving health of patients with diabetes and CHF is emphasized. Reports stating that nondiabetic CHF patients can have life-threatening hypoglycemia associated with imbalance of thyroid hormones are discussed. Regular glycemic control based on HbA1c measurements and adequate pharmacotherapy remain the priorities in diabetes management. New antihyperglycemic drugs with safer profiles should be preferred in vulnerable CHF patients. Multidrug interactions must be considered. Emerging therapies with reduced hypoglycemia risk, telemedicine, sensor technologies, and genetic testing predicting hypoglycemia risk may help solving the challenges of hypoglycemia in CHF patients with diabetes. Interdisciplinary work may involve cardiologists, diabetologists/endocrinologists, immunologists, gastroenterologists, microbiologists, nutritionists, imaging specialists, geneticists, telemedicine experts, and other relevant specialists. This review emphasizes that systematic knowledge on pathophysiology of hypoglycemia in diabetic patients with CHF is largely lacking and the gaps in our understanding require further discoveries.
... Reduced insulin clearance, slow gastric emptying, and decreased intestinal absorption of glucose are contributing factors. Reduction of gluconeogenesis and impairment of glycogenolysis and glucagon secretion prevent recovery from the hypoglycemia (6,7). Deficiency in cortisol, a counterregulatory hormone, can also cause hypoglycemia because of associated decreased gluconeogenesis and increased insulin sensitivity (4). ...
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A 35-year-old man known to have type 1 diabetes for 8 years presented to the emergency department with disturbed conscious level. He gave a history of recurrent similar attacks during the previous 8 months. All of these attacks were proved to be due to hypoglycemia. Some of the episodes were mild and treated by oral glucose only, whereas others were severe, requiring hospital admission and treatment with an intravenous glucose infusion. The patient had been taking human mixed insulin for the past 2 years. His insulin doses were reviewed by his primary care providers and decreased after each episode of hypoglycemia. His total daily insulin dose had been decreased from 70 to 10 units during the previous 8 months. The patient gave a history of darkening of the skin of his face and extremities associated with significant weight loss throughout the previous year. He had no family history of type 1 diabetes or thyroid or adrenal diseases. On admission to the emergency department, the patient had disturbed conscious level with no signs of lateralization. His blood pressure was 70/40 mmHg, pulse was 72 bpm and regular, weight was 60 kg, and BMI was 20.7 kg/m². Hyperpigmentation of the face, oral mucosa, and exposed areas of upper and lower limbs was evident, especially when compared to old photographs of the patient. No other significant clinical findings were noticed. His random blood glucose was 32 mg/dL. The patient was admitted to the intensive care unit. After receiving dextrose 25% intravenously, his conscious level improved significantly and was back to normal within 2 hours. Serum cortisol and free thyroxin (FT4) were very low. Thyroid-stimulating hormone (TSH) and adrenocorticotropic hormone (ACTH) were very high—150 mIU/mL (normal 0.35–5.5 mIU/mL) and 972 pg/mL (normal 10–46 pg/mL), respectively. Renal function was normal. Thyroid peroxidase (TPO) antibodies were highly positive. The patient was diagnosed to have polyglandular autoimmune syndrome type II (PAS II). He was started on hormonal replacement therapy (hydrocortisone before levothyroxine to avoid precipitating an adrenal crisis), with dose adjustments made during the following weeks. His general condition, blood pressure, and blood glucose showed significant improvement within 3 weeks. His insulin doses were gradually increased to achieve optimum blood glucose control.
... Hypoglycemia due to impaired gluconeogenesis, associated with thyroid dysfunction was presented in several reports. Abnormal glucagon response to hypoglycemia during hypothyroid state was reported as well [9]. ...
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Background: The interaction of zinc deficiency and hypothyroidism has several reported presentations. The link between hypoglycemia and hypothyroidism is also known, but uncommon. For the last 40 years, the relationship between these two phenomena was illustrated in a handful of articles. To the best of our knowledge, the sequence of hypoglycemia, hypothyroidism and zinc deficiency has not yet been reported. Case presentation: We present a six-month-old boy with the unusual combination of these three conditions, his diagnostic evaluation and management. Conclusion: We suggest that the relationship between zinc and thyroid function should be considered in any case of severe intractable hypoglycemia and extensive skin eruption.
Background: Decompensated hypothyroidism, formerly known as myxedema coma, is an endocrine emergency that commonly presents with altered mental status, as well as hypothermia and depressed vital signs. The condition is often caused by an inciting event, which may lead to significant delays in the diagnosis and management of this disease. Although the incidence is low, this disease is associated with significant morbidity and mortality. Therefore, it is important for emergency clinicians to be aware of this condition. Objective: This narrative review evaluates the emergency medicine diagnosis and management of adult patients with decompensated hypothyroidism. Discussion: Decompensated hypothyroidism is a severe hypothyroid state associated with multiple organ failure. The diagnosis can be challenging due to similarities with more common diseases and lack of consideration of the diagnosis. Many patients may present with altered sensorium or depressed vital signs. Clinicians should obtain a thyroid stimulating hormone and free thyroxine level when considering the diagnosis. Management involves resuscitation, early steroid supplementation, thyroid hormone replacement, and treatment of the inciting event. Conclusions: Decompensated hypothyroidism should be considered in the evaluation of patients with altered sensorium and depressed vital signs so as to not miss this critical diagnosis.
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Type 2 diabetes mellitus (DM) is a growing problem in our country and we have observed that many patients are associated with thyroid dysfunction later in their life. However, the prevalence of thyroid dysfunction in these patients has not been investigated. To find the prevalence of thyroid dysfunction in type 2 DM in Manipur, India. In this retrospective study, data of 202 Type 2 DM patients who attended the diabetic clinic of the Regional Institute of Medical Sciences, Imphal from January 2011 to July 2012, and whose thyroid stimulating hormone (TSH) level was investigated were included. The inclusion criteria are known cases of type 2 DM. Exclusion criteria are patients with previous history of hypothyroidism and those on drugs affecting the thyroid profile. Out the 202 type 2 DM patients for the study of which 61 are males and 141 are females, 139 (68.8%) are euthyroid, 33 (16.3%) have subclinical hypothyroidism (10 males and 23 females), 23 (11.4%) have hypothyroidism (6 males and 17 females), 4 (2%) have subclinical hyperthyroidism and 3 (1.5%) are hyperthyroidism cases. Maximum cases were of hypothyroidism (subclinical and clinical) seen in the age group of 45-64 years. Patients with BMI > 25 were at increased risk of having hypothyroidism (P < 0.016). Prevalence of hypothyroidism is quite high in type 2 DM patients above 45 years and more so if their BMI is over 25.
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The effect of thyroid status on insulin sensitivity is of great interest but despite various studies there is conflicting data on this subject. The study group comprised of 25 female subjects each with subclinical hypothyroidism, overt hypothyroidism and euthyroid controls. Serum samples of all the patients were assayed for thyroid profile, Insulin and lipid profile. Homeostasis model of assessment (HOMA-IR) was employed to assess the level of insulin resistance. Patients with hypothyroidism demonstrated insulin resistance and dyslipidemia as observed by the higher HOMA-IR and cholesterol and triglyceride levels respectively as compared to the controls. A significantly positive correlation between TSH and HOMA-IR level was also observed in the hypothyroidism group. Thyroid dysfunction leads to alterations in glucose and lipid metabolism which is an important risk factor for cardiovascular diseases. The dyslipidemia and insulin resistance should be managed aggressively to reduce the impending risk.
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Thyroid diseases are common worldwide. In India too, there is a significant burden of thyroid diseases. According to a projection from various studies on thyroid disease, it has been estimated that about 42 million people in India suffer from thyroid diseases. This review will focus on the epidemiology of five common thyroid diseases in India: (1) hypothyroidism, (2) hyperthyroidism, (3) goiter and iodine deficiency disorders, (4) Hashimoto's thyroiditis, and (5) thyroid cancer. This review will also briefly cover the exciting work that is in progress to ascertain the normal reference range of thyroid hormones in India, especially in pregnancy and children.
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Evidence for a relationship between T4 and T3 and glucose metabolism appeared over 100 years ago when the influence of thyroid hormone excess in the deterioration of glucose metabolism was first noticed. Since then, it has been known that hyperthyroidism is associated with insulin resistance. More recently, hypothyroidism has also been linked to decreased insulin sensitivity. The explanation to this apparent paradox may lie in the differential effects of thyroid hormones at the liver and peripheral tissues level. The purpose of this paper is to explore the effects of thyroid hormones in glucose metabolism and analyze the mechanisms whereby alterations of thyroid hormones lead to insulin resistance.
Objectives: This paper describes the prevalence of hypothyroidism, in young children and adolescents, aged less than 18 years, with type 1 diabetes mellitus, in northern India. Materials and Methods: Seventy patients (23 female, 47 male) were screened for hypothyroidism, using serum TSH, as part of a detailed assessment of the clinical profile of children and adolescents with type 1 diabetes in an endocrine centre located in Haryana, northern India. Results: Seven girls were found to have hypothyroidism of varying degree, and two boys had subclinical hypothyroidism. Conclusion: Thus, hypothyroidism is found to be a frequent association with type 1 diabetes mellitus in northern India.
IN BRIEF Although long-term maintenance of normoglycemia can prevent the onset and delay the progression of the microvascular complications in diabetes, a large percentage of diabetic patients continue to have poorly controlled glucose levels. The risk of hypoglycemia is a real obstacle to achieving glucose targets in type 1 diabetes. However, risk of severe hypoglycemia in type 2 diabetes is minimal and should not be used as an excuse for failing to achieve glycemic goals. This article reviews the incidence of severe hypoglycemia in the major diabetes trials, the results of attempts to optimize glycemia to date, and the ways to ameliorate severe hypoglycemia in the treatment of both type 1 and type 2 diabetes.
Background: Individual sulfonylurea agents differ in pharmacokinetic properties and clinical effects. This study aimed to describe the usage pattern, glycemic improvement, hypoglycemia, and change in body mass index (BMI) observed with commonly used sulfonylureas. Subjects and methods: Patients of either gender with type 2 diabetes mellitus (T2DM), between 18 and 75 years old and requiring addition of a sulfonylurea to an ongoing regimen of oral antihyperglycemic agent(s), were enrolled. Glycosylated hemoglobin (HbA1c) and BMI were assessed at both baseline and the end of 12 weeks of follow-up. The hypoglycemia score was assessed at the end of follow-up only. Results: In total, 1,069 patients were enrolled in the study, of whom 950 were considered evaluable. After a mean follow-up of 14.34±2.80 weeks, the HbA1c level decreased by 0.86±2.28%, BMI increased by 0.13±0.78 kg/m2, and mean hypoglycemia score was 0.98±1.42. A weak negative, statistically significant correlation (r = -0.093; P=0.0044) between hypoglycemic scores and increase in BMI was observed. No correlation was observed between change in HbA1c level and change in BMI. Glimepiride was the most commonly prescribed sulfonylurea (75.3%). For patients on glimepiride, a weak positive, statistically significant correlation (r=0.098; P=0.0082) between its dose and the hypoglycemic score was observed. Conclusions: Various sulfonylurea agents appear to differ in their effect on glycemic control, tendency to cause hypoglycemia, and gain in BMI. Hypoglycemia caused by these agents appears not only to be dose related, but also correlates inversely with gain in BMI.
We have previously reported that glucose production assessed using radioiso-topic methods is 50% increased in hyperthyroidism but 30% decreased in hypothyroidism. These studies, however, do not distinguish between glycogenolysis and gluconeogenesis. In fasting man more than 80% of circulating glycerol is cleared by the liver and enters the gluconeogenic pathway. We have therefore measured glycerol clearance following bolus intravenous glycerol administration as an indirect assessment of gluconeogenic capacity. Hyperthyroid and hypothyroid subjects were compared with separate matched controls after an overnight fast. In hyperthyroid subjects blood glucose and blood glycerol were increased but lactate, pyruvate, and alanine concentrations were normal. Glycerol clearance was increased in hyperthyroidism and followed a double exponential decay with a shortened second component half-time. Endogenous glycerol production was increased three-fold. In hypothyroidism fasting circulating levels of glucose, lactate, pyruvate, alanine, and glycerol were normal but glycerol clearance was diminished. Both first and second component half-times were prolonged in hypothyroidism and endogenous glycerol production was decreased by 50%. Thus in hyperthyroidism glycerol clearance is greatly enhanced whilst in hypothyroidism glycerol clearance is diminished. The magnitude of the changes suggests that alterations in gluconeogenesis are probably the major factors concerned in the reported increase and decrease in glucose production in hyperthyroidism and hypothyroidism respectively.