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Phenotypic Type 2 Diabetes in Obese Youth: Insulin Sensitivity and Secretion in Islet Cell Antibody-Negative Versus -Positive Patients

Authors:
Hala Tfayli at American University of Beirut
Hala Tfayli
Fida Bacha at Baylor College of Medicine
Fida Bacha
Neslihan Gungor at LSU HSC Shreveport
Neslihan Gungor
  • LSU HSC Shreveport
Silva Arslanian
Silva Arslanian
Silva Arslanian
  • This person is not on ResearchGate, or hasn't claimed this research yet.
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Abstract and Figures

Some obese youth with a clinical diagnosis of type 2 diabetes have evidence of islet cell autoimmunity with positive autoantibodies. In this study, we investigated the differences in insulin sensitivity and secretion between autoantibody-negative (Ab-) and -positive (Ab+) youth with clinically diagnosed type 2 diabetes in comparison with control subjects. Sixteen Ab- and 26 Ab+ clinically diagnosed type 2 diabetic patients and 39 obese control youth underwent evaluation of insulin sensitivity (3-h hyperinsulinemic-euglycemic clamp), substrate oxidation (indirect calorimetry), first- and second-phase insulin secretion (2-h hyperglycemic clamp), body composition and abdominal adiposity (dual energy X-ray absorptiometry and computed tomography scan, respectively), and glucose disposition index (first-phase insulin secretion x insulin sensitivity). Insulin-stimulated total, oxidative, and nonoxidative glucose disposal, and suppression of fat oxidation during hyperinsulinemia were significantly lower in Ab- compared with Ab+ clinically diagnosed type 2 diabetic and control subjects with no difference between the latter two. First- and second-phase insulin secretion and C-peptide were lower in Ab+ compared with Ab- type 2 diabetes. Glucose disposition index was not different between the Ab- and Ab+ clinically diagnosed type 2 diabetic patients, but both were significantly lower than that in control subjects. Systolic blood pressure and alanine aminotransferase were higher in Ab- versus Ab+ clinically diagnosed type 2 diabetic patients, whereas the frequency of ketonuria at diagnosis was higher in Ab+ versus Ab- patients. Islet-cell Ab- clinically diagnosed type 2 diabetic youth are characterized by severe insulin resistance and relative insulin deficiency, whereas Ab+ youth have severe insulin deficiency and beta-cell failure. The former group has additional features of insulin resistance. These important metabolic differences could influence the natural history of hyperglycemia, insulin dependence, and clinical outcomes in these youth.
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Phenotypic Type 2 Diabetes in Obese Youth: Insulin Sensitivity and Secretion in Islet Cell Antibody-Negative Versus -Positive Patien
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... Latent autoimmune diabetes in adults (LADA) shared biochemical markers of β-cell-directed autoimmunity with "classic" type 1diabetes i.e. documented by antibodies against GAD and treated with insulin earlier than in those with nonautoimmune diabetes mellitus [13]. Insulin sensitivity was severely impaired in autoantibodies negative (Ab − ) but not autoantibodies positive (Ab + ) patients and β-cell function was almost completely abolished in Ab + and not Ab − type 2 diabetes [14]. Moreover, the Ab − clinical diagnosis -type 2 diabetic patients had features consistent with the metabolic syndrome. ...
... Moreover, the Ab − clinical diagnosis -type 2 diabetic patients had features consistent with the metabolic syndrome. Islet-cell Ab − clinically diagnosed type 2 diabetic youth are characterized by severe insulin resistance and relative insulin deficiency, whereas Ab + youth have severe insulin deficiency and β-cell failure [14]. This comparative study is aimed to explore the differences in the biochemical and immunological indexes in poorly controlled diabetics with (Ab − ) and (Ab + ) type 1 and clinically diagnosed type 2 diabetes. ...
Evaluation of signs of immune or metabolic disturbances among diabetic patients with positive islet cell antibodies
Article
  • Apr 2012
Background: Autoantibodies to islet cell antigens are known predictors of type 1 diabetes and detected in latent autoimmune diabetes in adults.Objectives: This study aimed to identify the metabolic and immunological disturbances in diabetic patients with positive and negative islet cell antibodies (ICAs)Materials and methods: A total number of 235 known cases of diabetes mellitus type 1 (160) and type 2 diabetes (75) were admitted in the study. Serum ICA and immunoglobulins (IgA, IgM, IgG) as well lipid profile were measured.Results: Positive ICAs was found in 40 out of 120 T1D (33.3%) and 28 out of 75 T2D (37.3%). All the patients were poorly controlled diabetes with the evidence of significant high HbA1c%. There were no significant differences in the lipid profile or immunoglobulin levels between positive and negative ICAs in T1D and T2D.Conclusions: Autoimmunity in term of positive ICA does not play a role in metabolic or immunologic disturbances that associated with T1D and T2D.
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... Yoon et al. [20] reported that despite the average BMI in Asian children being lower than that of European children, Asian children had higher prevalence of type 2 diabetes. As a possible explanation, it has been speculated that for the same BMI, Asian children might have a greater amount of VF than children of European descent [21,22]. ...
... Meanwhile, Yoon et al. [20] found that Asians had a higher prevalence of type 2 diabetes than Europeans, despite a lower of prevalence of obesity, suggesting Asians are likely to develop glucose intolerance though they are non-obese. Sex and some ethnic factors [21,22] might contribute to the development of type 2 diabetes in non-obese individuals. ...
Pathophysiological significance in abdominal fat distribution in non-obese children with type 2 diabetes
Article
  • Feb 2023
The aim of the study was to determine the pathogenesis of non-obese children with type 2 diabetes, and its relationship with fat distribution. The study participants included 36 obese children with type 2 diabetes (age: 13.5 years, BMI: 28.3, BMI percentile: 91.9) and 30 non-obese children with type 2 diabetes (age: 13.5 years, BMI: 23.1, BMI percentile: 74.0). The proportion of female participants was significantly higher in non-obese children than in obese children (73.3% vs. 41.7%, p < 0.001). Abdominal fat distribution, evaluated by subcutaneous fat (SF) area, visceral fat (VF) area, and the ratio of VF area to SF area (V/S ratio), measured using computed tomography, and serum lipid levels and liver function were compared between the two groups. Non-obese children with type 2 diabetes had significantly smaller SF area and also smaller VF area than obese children with type 2 diabetes (SF area: 158.3 m² vs. 295.3 m², p < 0.001, VF area: 71.0 m² vs. 94.7 m², p = 0.032). Whereas non-obese children with type 2 diabetes had significantly greater V/S ratio than obese children with type 2 diabetes (0.41 vs. 0.31, p = 0.007).The prevalence of dyslipidemia and liver dysfunction were similar in the two groups. In conclusion, non-obese children with type 2 diabetes had excess accumulation of VF despite a small amount of SF, which might be associated with glucose intolerance and other metabolic disorders.
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... Diabetes mellitus is a long-term disorder of the metabolism of carbohydrates, proteins, and fats arising from a deficiency of insulin, insulin resistance, or both, leading to hyperglycaemia ( Tfayli et al., 2009 ). It is one of the most disturbing and common chronic diseases of our times, causing life-threatening, disabling, and costly complications and reducing life expectancy ( Aamir et al., 2020 ). ...
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... 97,[100][101][102][103][104] Patients with positive autoimmunity have more severe insulin deficiency compared with patients with autoantibody-negative T2D, who are more likely to have severe insulin resistance. 105 The pathogenic mechanisms driving diabetes in these 2 subgroups may be different and need further study. ...
The Prevalence of Obesity Among Children With Type 2 Diabetes: A Systematic Review and Meta-analysis
Article
Full-text available
  • Dec 2022
Importance The childhood obesity epidemic is presumed to drive pediatric type 2 diabetes (T2D); however, the global scale of obesity in children with T2D is unknown. Objectives To evaluate the global prevalence of obesity in pediatric T2D, examine the association of sex and race with obesity risk, and assess the association of obesity with glycemic control and dyslipidemia. Data Sources MEDLINE, Embase, CINAHL, Cochrane Library, and Web of Science were searched from database inception to June 16, 2022. Study Selection Observational studies with at least 10 participants reporting the prevalence of obesity in patients with pediatric T2D were included. Data Extraction and Synthesis Following the Meta-analysis of Observational Studies in Epidemiology reporting guideline, 2 independent reviewers in teams performed data extraction and risk of bias and level of evidence analyses. The meta-analysis was conducted using a random-effects model. Main Outcomes and Measures The primary outcomes included the pooled prevalence rates of obesity in children with T2D. The secondary outcomes assessed pooled prevalence rates by sex and race and associations between obesity and glycemic control and dyslipidemia. Results Of 57 articles included in the systematic review, 53 articles, with 8942 participants, were included in the meta-analysis. The overall prevalence of obesity among pediatric patients with T2D was 75.27% (95% CI, 70.47%-79.78%), and the prevalence of obesity at diabetes diagnosis among 4688 participants was 77.24% (95% CI, 70.55%-83.34%). While male participants had higher odds of obesity than female participants (odds ratio, 2.10; 95% CI, 1.33-3.31), Asian participants had the lowest prevalence of obesity (64.50%; 95% CI, 53.28%-74.99%), and White participants had the highest prevalence of obesity (89.86%; 95% CI, 71.50%-99.74%) compared with other racial groups. High heterogeneity across studies and varying degrees of glycemic control and dyslipidemia were noted. Conclusions and Relevance The findings of this systematic review and meta-analysis suggest that obesity is not a universal phenotype in children with T2D. Further studies are needed to consider the role of obesity and other mechanisms in diabetes genesis in this population.
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... It was also suggested that the degree of obesity might be associated with the risk of developing islet autoantibodies in adults with T2D -among 204 patients with T2D and excess body weight, the presence of at least one of the three antibodies (GADA, IA2, and ZnT8A) was found in 6.4% of all subjects and in as many as 12.8% when considering those with severe obesity (BMI > = 40 kg/ m2) (29). On the other hand, studies on pediatric patients with T2D reported the presence of at least one anti-islet antibody in approximately 30% of them (11,(30)(31)(32). The presence of at least one anti-islet antibody (GADA or IA2) in obese children with T2D was associated with younger age, lower insulin secretion, higher HbA1c, and a higher incidence of diabetic ketoacidosis at diagnosis (33). ...
Autoimmune reaction against pancreatic beta cells in children and adolescents with simple obesity
Article
Full-text available
  • Dec 2022
Introduction One of the most important complications of obesity is insulin resistance, which leads to carbohydrate metabolism disorders such as type 2 diabetes. However, obesity is also associated with development of an autoimmune response against various organs, including pancreatic beta cells. The prevalence of such autoimmune processes in children and their possible contribution to the increased incidence of type 1 diabetes is currently unclear. Therefore, the present study assessed the prevalence of autoantibodies against pancreatic islet beta cell’s antigens in children and adolescents with simple obesity. Material and methods This prospective observational study included pediatric patients (up to 18 years of age) with simple obesity hospitalized between 2011 and 2016 at the Department of Pediatrics, Diabetology, Endocrinology and Nephrology of the Medical University of Lodz. Children with acute or chronic conditions that might additionally affect insulin resistance or glucose metabolism were excluded. Collected clinical data included sex, age, sexual maturity ratings (Tanner`s scale), body height and weight, waist and hip circumference, amount of body fat and lean body mass. Each participant underwent a 2-hour oral glucose tolerance test with simultaneous measurements of glycaemia and insulinemia at 0`, 60` and 120`. In addition, glycated hemoglobin HbA1c, fasting and stimulated c-peptide, total cholesterol, as well as high- and low-density cholesterol and triglycerides were measured. Insulin resistance was assessed by calculating HOMA-IR index. The following autoantibodies against pancreatic islet beta cells were determined in each child: ICA - antibodies against cytoplasmic antigens of pancreatic islets, GAD - antibodies against glutamic acid decarboxylase, ZnT8 - antibodies against zinc transporter, IA2 - antibodies against tyrosine phosphatase, IAA – antibodies against insulin. Results The study group included 161 children (57.4% boys, mean age 13.1 ± 2.9 years) with simple obesity (mean BMI z-score +2.2 ± 1.6). Among them, 28 (17.4%) were diagnosed with impaired glucose metabolism during OGTT [23 (82.2%) – isolated impaired glucose tolerance (IGT), 3 (10.7%) – isolated impaired fasting glucose (IFG), 2 (7.1%) – IFG and IGT]. Of the children tested, 28 (17.4%) were tested positive for at least one islet-specific autoantibody [with similar percentages in boys (15, 17.4%) and girls (13, 17.3%), p=0.9855], with ICA being the most common (positive in 18, 11.2%), followed by IAA (7, 4.3%), ZnT8 (5, 3.1%), GADA (3, 1.9%) and IA2 (1, 0.6%). There was no association between the presence of the tested antibodies and age, sex, stage of puberty, parameters assessing the degree of obesity, HbA1c, lipid levels and basal metabolic rate. However, autoantibody-positive subjects were more likely to present IFG or IGT in OGTT compared to those who tested completely negative (9, 32.1% vs 19, 14.3%, p=0.0280). Their HOMA-IR was also significantly higher (HOMA-IR: 4.3 ± 1.9 vs 3.4 ± 1.9, p=0.0203) and this difference remained statistically significant after adjusting for sex and age (p=0.0340). Conclusions Children and adolescents with simple obesity presented a higher prevalence of markers of autoimmune response against pancreatic beta cells than the general population. Most often, they had only one type of antibody - ICA. The presence of autoimmune response indicators against pancreatic islet antigens is more common in obese patients with impaired carbohydrate metabolism and is associated with lower insulin sensitivity.
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... The onset characteristics of LADY are similar to those of LADA and include noninsulindependent diabetes with beta cell autoantibodies and similar early clinical manifestations to T2DM. Studies have shown important differences in insulin sensitivity, insulin secretion metabolism, therapy method, susceptible human leukocyte antigen (HLA) genetic load and cytokine levels between LADY and youth T2DM patients (8)(9)(10), which deepens our knowledge of LADY. However, few studies have reported the incidence of comorbidities in LADY patients. ...
Thyroid autoantibody distribution in patients with latent autoimmune diabetes in youth: a multicenter, national survey
Article
Full-text available
  • Aug 2022
Background: A high seropositive rate of thyroid autoantibodies is often reported in patients with type 1 diabetes mellitus (T1DM), latent autoimmune diabetes in adults (LADA) and type 2 diabetes mellitus (T2DM). However, the positive rate of thyroid autoantibodies in latent autoimmune diabetes in youth (LADY) patients has not been reported in China. Thus, the purpose of the current study was to clarify the thyroid autoantibody distribution in patients with LADY to provide evidence for the clinical screening of autoimmune thyroid diseases (AITD). Methods: This nationwide, multicenter and cross-sectional study included 1,723 younger patients (<30 years old) and 2,000 older patients (≥30 years old) aged 15 to 79 years. The patients were grouped into younger T1DM (n=281), LADY (n=130), younger T2DM (n=200), older T1DM (n=287), LADA (n=129), and older T2DM (n=200) groups. Autoantibodies against thyroid peroxidase (TPOA) and thyroglobulin (TGA) prevalence were analyzed in each group. Results: The prevalence of TGA or TPOA in LADY patients was similar to that in younger T1DM patients. The seropositive rate of TPOA in LADY patients was higher than that in LADA patients (36.2% vs. 23.3%, respectively; P=0.023); the risk of TPOA was higher in LADY patients than in LADA patients, even after adjusting for sex, glutamic acid decarboxylase (GADA)- and insulinoma-associated-2 (IA-2A)-positivity (OR =1.94, P=0.023). LADY patients with high GADA titers exhibited a higher frequency of thyroid autoantibodies than patients with low GADA titers did (TPOA, P=0.005; TGA, P=0.023; TPOA or TGA, P=0.004). Further analysis showed that only male patients showed a strong association between high GADA titers and thyroid autoantibodies positivity, and the association remained significant after adjustment for age (OR =11.14, P=0.025 for TGA; OR =4.99, P=0.011 for TPOA; OR =5.52, P=0.007 for TPOA or TGA). Conclusions: Routine screening for thyroid autoantibodies is recommended in LADY patients, and special clinical attention should be paid to the thyroid autoantibodies status of male patients of LADY with high GADA titers to identify patients at high risk of developing AITD.
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Pancreatic autoantibodies in individuals with a clinical diagnosis of type 2 diabetes mellitus
Article
  • Sep 2023
Objectives It can be challenging to accurately diagnose type 2 diabetes (T2D) in children based on clinical features alone. We aimed to describe pediatric patients with a clinical diagnosis of T2D who are positive for pancreatic autoantibodies and compare their clinical features to patients with T2D without autoantibodies. Material and Methods This cross-sectional study and medical record review included patients aged 10–30 years with T2D seen at our pediatric diabetes clinic between January 01, 2013, and December 31, 2020. We compared the characteristics of autoantibody-positive patients with autoantibody-negative patients using Chi-square tests for binary variables and t -tests for continuous variables. Results Eleven out of 87 (12.6%) patients with a clinical diagnosis of T2D had positive autoantibody results. The groups with and without antibodies were not significantly different in terms of age, sex, and body mass index (BMI) Z-score. However, the hemoglobin A1c (HbA1c) closest to the time of the first autoantibody test was significantly lower in the autoantibody-positive group. Two of the 11 antibody-positive patients had two positive autoantibodies and one had four positive autoantibodies. The other eight patients were positive for one autoantibody only. One of the 11 antibody-positive patients had an episode of diabetic ketoacidosis (DKA). Conclusion While age, sex, and BMI were similar in both groups, patients with autoantibodies had significantly lower HbA1c at the time of antibody testing and one patient went into DKA. Autoantibodies should be measured in all patients diagnosed with diabetes to avoid the consequences of potential misclassification.
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Approach to the Patient with Youth-Onset Type 2 Diabetes
Article
  • Aug 2023
  • J CLIN ENDOCR METAB
Youth-onset type 2 diabetes is a growing epidemic with a rising incidence worldwide. Although the pathogenesis and diagnosis of youth-onset type 2 diabetes are similar to adult-onset type 2 diabetes, youth-onset type 2 diabetes is unique, with greater insulin resistance, insulin hypersecretion, and faster progression of pancreatic beta cell function decline. Individuals with youth-onset type 2 diabetes also develop complications at higher rates within short periods of time compared to adults with type 2 diabetes or youth with type 1 diabetes. The highest prevalence and incidence of youth-onset type 2 diabetes in the United States is among youth from minoritized racial and ethnic groups. Risk factors include obesity, family history of type 2 diabetes, co-morbid conditions and use of medications associated with insulin resistance and rapid weight gain, socio-economic and environmental stressors, and birth history of small-for-gestational-age or pregnancy associated with gestational or pre-gestational diabetes. Patients with youth-onset type 2 diabetes should be treated using a multi-disciplinary model with frequent clinic visits and emphasis on addressing of social and psychological barriers to care, glycemic control, as well as close monitoring for comorbidities and complications. Intensive health behavior therapy is an important component of treatment, in addition to medical management, both of which should be initiated at the diagnosis of type 2 diabetes. There are limited but growing pharmacologic treatment options including metformin, insulin, glucagon-like peptide 1 receptor agonists, and sodium-glucose cotransporter 2 inhibitors. Although long-term outcomes are not fully known, metabolic/bariatric surgery in youth with type 2 diabetes has led to improved cardiometabolic outcomes.
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Journal Pre-proof Evaluation of the Antidiabetic activity and Toxicological properties of Hippocratea Velutina (Afzel.) Evaluation of the Antidiabetic activity and Toxicological properties of Hippocratea Velutina (Afzel.)
Preprint
Full-text available
  • Jan 2023
Background Hippocratea velutina (HV) is a novel plant folklorically used for lowering blood glucose, hence a potential source of new antidiabetic medication. Objective The study evaluated the anti-diabetic potentials of the methanol extract of Hippocratea velutina leaf and its toxicity profile in mice and rats. Methods Acute and subacute toxicity tests of the plant extract were carried out using a modified OECD guideline. Its antidiabetic activity in streptozotocin-induced diabetic rats at 50, 150, and 300 mg/kg for 28 days was assayed, while glibenclamide (5 mg/kg) and distilled water were the positive and negative controls, respectively. Histopathological examination of vital organs was also carried out. Results Preliminary phytochemical screening of the leaf extract showed the presence of tannins, flavonoids, saponins, alkaloids, terpenoids, deoxy-sugars, and anthraquinones in HV. The extract had LD50 greater than 2000 mg/kg in mice. It had no toxic effects on the haematological and biochemical components from blood samples collected but caused significant blood glucose level reduction in normal rats at 150 and 300 mg/kg. In streptozotocin-induced diabetic rats, the extract elicited a non–dose-dependent antidiabetic effect on day seven at all the tested doses, significantly higher than glibenclamide (10 mg/kg). However, on days 14, 21, and 28, the extract activity at all the tested doses and glibenclamide were comparable. The extract did not affect the liver, brain, kidney, and pancreas histology at 200 mg/kg but caused slight and severe effects on these organs at 400 and 800 mg/kg, respectively. Conclusion The study concluded that Hippocratea velutina possessed antihyperglycaemic activity and is non-toxic at low doses but could have deleterious effects to the liver and kidney at high concentrations.
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Clinical characteristics and cardiovascular risk profile in children and adolescents with latent autoimmune diabetes (LADY): results from the German/Austrian Prospective Diabetes Follow-up Registry
Article
Aims: To characterize children and adolescents with latent autoimmune diabetes of the young (LADY), and to assess the utility of classifying individuals as LADYs regarding their cardiovascular (CV) risk factors. Methods: Data from 25,520 individuals (age at diagnosis <18 years) of the Prospective Diabetes Follow-up Registry Diabetes-Patienten Verlaufsdokumentation (DPV) were analysed. LADY was defined as positivity of ≥one islet autoantibody (iAb+) and an insulin-free interval of ≥6 months upon diabetes diagnosis. LADYs were compared to iAb+ individuals immediately requiring insulin ("immunologically confirmed" type 1 diabetes, T1DM), iAb-/Ins- individuals ("classical" T2DM) and to those clinically defined as T2DM (iAbs not measured). Results: Clinical characteristics of LADYs (n=299) fell in between those with T1DM (n=24,932) and T2DM (iAb-/Ins-, n=152) or suspected T2DM (iAB not measured, n=137). Stratifying LADYs according to their clinical diagnosis however revealed two distinct populations, highly resembling either T1DM or T2DM. Particularly, CV risk profile, precisely prevalence rates of arterial hypertension and dyslipidemia, was significantly higher in LADYs clinically classified as T2DM compared to LADYs classified as T1DM, and did not differ from those with "classical" T2DM. Conclusions: In terms of CV risk, classifying children and adolescents with diabetes as LADYs provides no additional benefit. Instead, clinical diagnosis seems to better assign individuals to appropriate risk groups for increased CV risk profiles. This article is protected by copyright. All rights reserved.
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Treatment of type 2 diabetes mellitus in children and adolescents
Conference Paper
  • Dec 2000
The treatment of type 2 diabetes mellitus (DM) is directed at decreasing insulin resistance and increasing insulin secretion. alpha -Glucosidase inhibitors slow carbohydrate absorption, resulting in reduced postprandial hyperglycemia; thiazolidinediones increase insulin sensitivity, especially in muscle and adipocytes; metformin decreases hepatic gluconeogenesis; sulfonylureas result in prolonged increases in insulin secretion; and meglitinide causes rapid, short-lived increases in insulin secretion, A survey of 130 pediatric endocrinology practices in the USA and Canada indicated that 48% of children with type 2 DM were treated with insulin and 44% with one or more oral hypoglycemic agents (OHA). Of those treated with OHA, 71% received metformin, 46% sulfonylureas, 9% thiazolidinediones and 4% meglitinide, Similarly, in the three university-based diabetes centers in Florida, 50% of the children with type 2 DM were treated with OHA. Treatment is based on symptoms at presentation. Patients identified on routine testing are often treated with exercise and diet alone. Those who are mildly symptomatic at onset are often started on OHA, Patients with substantial ketosis, ketoacidosis or markedly elevated blood glucose levels are initially treated with insulin, followed by a tapering of the dose and the addition of an OHA after blood glucose control is established and symptoms subside. There are no studies of the efficacy or compliance with treatment for type 2 DM in adolescents. Treatment is currently based on the clinical experience with adults. Controlled clinical trials in children are essential.
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SEARCH for Diabetes in Youth: a multicenter study of the prevalence, incidence and classification of diabetes mellitus in youth
Article
  • Oct 2004
  • Contr Clin Trials
SEARCH for Diabetes in Youth is an observational, multicenter study focusing on physician-diagnosed diabetes in individuals <20 years old. The study will estimate the population prevalence and incidence of diabetes by type, age, gender, and ethnicity and develop practical approaches to diabetes classification in 5 million children (similar to6% of the <20 U.S. population) with wide ethnic and socioeconomic representation from four geographically defined populations and two health plans. An estimated 6000 prevalent and 800 incident diabetes cases per year will be identified with annual follow-up. Cases will be ascertained through clinical and nonclinical resources or partnerships at each site. Data collection involves patient interviews, physical examinations, laboratory measurements (diabetes autoantibodies, fasting/stimulating C-peptide, hemoglobin A1c, blood glucose, lipids, urine albumin, creatinine), medical records reviews, and documentation of risk factors for complications and processes of care.
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Assessment of Growth and Maturation during Adolescence
Article
  • Feb 1993
Clinical techniques currently used to assess adolescent growth and maturation are critically assessed with regard to anthropometric dimensions, measurement reliability, maturity indicators, and growth standards. While anthropometric measurements are virtually standardized throughout the world, a choice of techniques is available for the assessment of skeletal maturity, dental maturity and secondary sexual development. In addition, a variety of charts of international and national reference data are available for the comparison of individuals and groups. These assessment and comparison techniques are contrasted and compared to arrive at a scientifically appropriate set of recommendations for the clinical assessment of growth and maturity during adolescence.
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Pathogenic factors of glucose intolerance in obese Japanese adolescents with type 2 diabetes
Article
  • Feb 2000
  • METABOLISM
We attempted to identify the pathogenic factors involved in the progression to type 2 diabetes in obese Japanese adolescents. Subjects included 18 nondiabetic obese adolescents, 12 obese adolescents with type 2 diabetes on diet therapy, 10 obese adolescents with type 2 diabetes manifesting ketosis at onset or with a history of treatment with hypoglycemic agents, and 26 non-obese adolescent control subjects. The first-phase insulin response (FPIR), glucose disappearance constant (Kg), glucose effectiveness (Sg), and insulin sensitivity (S(I)) were obtained using an insulin-modified frequently sampled intravenous glucose tolerance test (FSIGT) and a minimal model analysis. The disposition index (DI, by FPIR x S(I)) was determined to assess any endogenous insulin effect. The results showed that Kg was decreased significantly (P = .0006) with the progression to severe diabetes in the obese groups. Although S(I) and Sg did not differ significantly among the 3 obese groups, both parameters were significantly lower in each obese group versus the non-obese controls. As a result of the significant decrease in FPIR (P < .0001), the DI decreased (P = .0006) with the progression to severe diabetes in the obese groups. In conclusion, an early manifestation of type 2 diabetes with occasional ketosis at onset may result from beta-cell dysfunction to glucose stimulation. This finding is demonstrated by the relatively low FPIR to decreased S(I) in obese Japanese adolescents, as well as the low Sg as a synergic role in glucose intolerance. The present findings from a Japanese population for pathogenic factors aside from obesity may help us to gain a better understanding of the progression to adolescent, early-onset, obese type 2 diabetes and its severity.
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