Harish Ranjani

Evidence of reduced β-cell function in Asian Indians with mild dysglycemia.

OBJECTIVE To examine β-cell function across a spectrum of glycemia among Asian Indians, a population experiencing type 2 diabetes development at young ages despite low BMI. RESEARCH DESIGN AND METHODS One-thousand two-hundred sixty-four individuals without known diabetes in the Diabetes Community Lifestyle Improvement Program in Chennai, India, had a 75-g oral glucose tolerance test, with glucose and insulin measured at 0, 30, and 120 min. Type 2 diabetes, isolated impaired fasting glucose (iIFG), isolated impaired glucose tolerance (iIGT), combined impaired fasting glucose and impaired glucose tolerance, and normal glucose tolerance (NGT) were defined by American Diabetes Association guidelines. Measures included insulin resistance and sensitivity (homeostasis model assessment of insulin resistance [HOMA-IR], modified Matsuda Index, 1/fasting insulin) and β-cell function (oral disposition index = [Δinsulin0–30/Δglucose0–30] × [1/fasting insulin]). RESULTS Mean age was 44.2 years (SD, 9.3) and BMI 27.4 kg/m2 (SD, 3.8); 341 individuals had NGT, 672 had iIFG, IGT, or IFG plus IGT, and 251 had diabetes. Patterns of insulin resistance or sensitivity were similar across glycemic categories. With mild dysglycemia, the absolute differences in age- and sex-adjusted oral disposition index (NGT vs. iIFG, 38%; NGT vs. iIGT, 32%) were greater than the differences in HOMA-IR (NGT vs. iIFG, 25%; NGT vs. iIGT, 23%; each P < 0.0001). Compared with NGT and adjusted for age, sex, BMI, waist circumference, and family history, the odds of mild dysglycemia were more significant per SD of oral disposition index (iIFG: odds ratio [OR], 0.36; 95% CI, 0.23–0.55; iIGT: OR, 0.37; 95% CI, 0.24–0.56) than per SD of HOMA-IR (iIFG: OR, 1.69; 95% CI, 1.23–2.33; iIGT: OR, 1.53; 95% CI, 1.11–2.11). CONCLUSIONS Asian Indians with mild dysglycemia have reduced β-cell function, regardless of age, adiposity, insulin sensitivity, or family history. Strategies in diabetes prevention should minimize loss of β-cell function.

A model of translational research for diabetes prevention in low and middle-income countries: The Diabetes Community Lifestyle Improvement Program (D-CLIP) trial

AIMS The Diabetes Community Lifestyle Improvement Program (D-CLIP) aims to implement and evaluate in a controlled, randomized trial the effectiveness, cost-effectiveness, and sustainability of a culturally appropriate, low-cost, and sustainable lifestyle intervention for the prevention of type 2 diabetes mellitus in India. METHODS D-CLIP, a translational research project adapted from the methods and curriculum developed and tested for efficacy in the Diabetes Prevention Program, utilizes innovated methods (a step-wise model of diabetes prevention with lifestyle and metformin added when needed; inclusion of individuals with isolated glucose tolerance, impaired fasting glucose, and both; classes team-taught by professionals and trained community educators) with the goals of increasing diabetes prevention, community acceptability, and long-term dissemination and sustainability of the program. The study outcomes are: diabetes incidence (primary measure of effectiveness), cost-effectiveness, changes in anthropometric measures, plasma lipids, blood pressure, blood glucose, and HbA(1c,) Program acceptability and sustainability will be assessed using a mixed methods approach. CONCLUSION D-CLIP, a low-cost, community-based, research program, addresses the key components of translational research and can be used as a model for prevention of chronic diseases in other low and middle-income country settings.

Decreased prevalence of lymphatic filariasis among subjects with type-1 diabetes

Several animal studies have shown a protective effect of helminth infections against type-1 diabetes mellitus (T1DM). However, epidemiologic studies demonstrating this protective relationship with T1DM are largely lacking, although an inverse correlation between the prevalence of lymphatic filariasis (LF) and prevalence of allergies and autoimmunity has been shown. A cross-sectional study was undertaken in southern India to assess the baseline prevalence of seropositivity of LF among persons with T1DM (n = 200) and normal glucose tolerant (NGT) persons (n = 562). The prevalence of LF was 0% among persons with T1DM and 2.6% among NGT persons (P = 0.026). The percentage of persons who were positive for filarial antigen-specific IgG4 (but not antigen-specific IgG) was also significantly lower in persons with T1DM (2%) compared with NGT persons (28%) (P < 0.001). Thus, there appears to be a striking inverse relationship between the prevalence of LF and T1DM in southern India.

Associations of β-Cell Function and Insulin Resistance with Youth-Onset Type 2 Diabetes and Prediabetes Among Asian Indians

AIM This study examined β-cell function and insulin resistance (homeostasis model assessment-insulin resistance [HOMA-IR]) in Asian Indian youth with type 2 diabetes mellitus (T2DM-Y) and prediabetes. SUBJECTS AND METHODS Eighty-two subjects with non-insulin-requiring type 2 diabetes and age of onset below 25 years were recruited within 18 months of diagnosis and compared with age- and sex-matched subjects with prediabetes (n=31) and normal glucose tolerance (NGT) (n = 83). Body mass index (BMI) and waist circumference were measured, and blood samples were taken in the fasting state and after 30, 60, 90, and 120 min of an oral glucose load for assessment of plasma glucose and insulin levels. Insulin sensitivity/resistance measures was calculated by using the reciprocal of the fasting insulin, the HOMA-IR equation, and the composite whole body insulin sensitivity index (Matsuda Index), and β-cell function was calculated by the oral disposition index (DIo). RESULTS T2DM-Y and prediabetes subjects had higher BMI, waist circumference, and fasting insulin than NGT subjects (P<0.05 for each). The 30-min insulin levels were lower in T2DM-Y and higher in prediabetes subjects compared with NGT (57 and 140 vs. 129 μIU/mL, P<0.001). The T2DM-Y group had greater insulin resistance (HOMA-IR, 1.87 vs. 0.97; P<0.05) and lower β-cell function (DIo, 0.36 vs. 3.28; P<0.001) than NGT. In separate models, the Matsuda Index and DIo were independently associated with prediabetes and T2DM-Y (P<0.05). However, when both were included together, only DIo remained associated with T2DM-Y, whereas both DIo and Matsuda Index were associated with prediabetes (P<0.05). When controlled for adiposity (BMI and waist circumference), an association was observed but in opposite directions, with waist being positively associated with prediabetes (P = 0.016) and BMI negatively associated with T2DM-Y (P = 0.009). CONCLUSIONS Among Asian Indians, β-cell dysfunction appears to be more strongly associated with T2DM-Y than insulin resistance.

The Stepwise Approach to Diabetes Prevention: Results From the D-CLIP Randomized Controlled Trial

OBJECTIVE This study tests the effectiveness of expert guidelines for diabetes prevention: lifestyle intervention with addition of metformin, when required, among people with prediabetes. RESEARCH DESIGN AND METHODS The Diabetes Community Lifestyle Improvement Program (D-CLIP) is a randomized, controlled, translation trial of 578 overweight/obese Asian Indian adults with isolated impaired glucose tolerance (iIGT), isolated impaired fasting glucose (iIFG), or IFG+IGT in Chennai, India. Eligible individuals were identified through community-based recruitment and randomized to standard lifestyle advice (control) or a 6-month, culturally tailored, U.S. Diabetes Prevention Program–based lifestyle curriculum plus stepwise addition of metformin (500 mg, twice daily) for participants at highest risk of conversion to diabetes at ≥4 months of follow-up. The primary outcome, diabetes incidence, was assessed biannually and compared across study arms using an intention-to-treat analysis. RESULTS During 3 years of follow-up, 34.9% of control and 25.7% of intervention participants developed diabetes (P = 0.014); the relative risk reduction (RRR) was 32% (95% CI 7–50), and the number needed to treat to prevent one case of diabetes was 9.8. The RRR varied by prediabetes type (IFG+IGT, 36%; iIGT, 31%; iIFG, 12%; P = 0.77) and was stronger in participants 50 years or older, male, or obese. Most participants (72.0%) required metformin in addition to lifestyle, although there was variability by prediabetes type (iIFG, 76.5%; IFG+IGT, 83.0%; iIGT, 51.3%). CONCLUSIONS Stepwise diabetes prevention in people with prediabetes can effectively reduce diabetes incidence by a third in community settings; however, people with iIFG may require different interventions.

Prevalence and risk factors for diabetic retinopathy in Asian Indians with young onset Type 1 and Type 2 Diabetes

AIM To assess the prevalence and risk factors for diabetic retinopathy (DR) in people with young onset type 1 (T1DM-Y) and type 2 diabetes (T2DM-Y). METHODS T1DM-Y(n=150) and T2DM-Y(n=150) participants, age between 10 and 25 years at diagnosis, had a complete clinical evaluation, biochemical assessment, and four field digital retinal colour photography. The Early Treatment Diabetic Retinopathy Study grading system was used to grade DR. Proliferative diabetic retinopathy (PDR) and diabetic macular edema (DME) were considered as sight threatening DR. RESULTS The prevalence of any DR was 53.3% [95% CI 45.3-61.3] in T1DM-Y (duration of diabetes: 12.4±7.4 years) and 52.7% [44.7-60.7] in T2DM-Y (11.8±8.3 years). The age and gender adjusted prevalence of DR, DME and PDR was 62.5%, 10% and 7.3% in T1DM-Y, whereas it was 65.8%,12.7% and 9.3% in T2DM-Y respectively. In multivariable logistic regression, diabetes duration [Odds ratio (OR) 1.99 per 5 years; CI 1.42-2.79], waist circumference [1.28 per 5 cm;1.05-1.56] and microalbuminuria [2.39 per 50 μg;1.07-5.31] were associated with DR in T1DM-Y, and diabetes duration [2.21 per 5 years; 1.61-3.02], diastolic blood pressure [1.54 per 5 mmHg;1.18-2.02], Glycated hemoglobin [1.37 per %;1.07-1.75] and lower stimulated C-peptide [1.54 per 0.5 pmol/ml;1.15-2.05;] were associated with DR in T2DM-Y. CONCLUSION Over half of the people with young-onset diabetes, regardless of type, have retinopathy within 10-12 years of diabetes duration, emphasizing the need for regular eye screening and aggressive control of glucose and blood pressure to prevent DR.

Epidemiology of childhood overweight & obesity in India: A systematic review

Background & objectives: Childhood obesity is a known precursor to obesity and other non-communicable diseases (NCDs) in adulthood. However, the magnitude of the problem among children and adolescents in India is unclear due to paucity of well-conducted nationwide studies and lack of uniformity in the cut-points used to define childhood overweight and obesity. Hence an attempt was made to review the data on trends in childhood overweight and obesity reported from India during 1981 to 2013. Methods: Literature search was done in various scientific public domains from the last three decades using key words such as childhood and adolescent obesity, overweight, prevalence, trends, etc. Additional studies were also identified through cross-references and websites of official agencies. Results: Prevalence data from 52 studies conducted in 16 of the 28 States in India were included in analysis. The median value for the combined prevalence of childhood and adolescent obesity showed that it was higher in north, compared to south India. The pooled data after 2010 estimated a combined prevalence of 19.3 per cent of childhood overweight and obesity which was a significant increase from the earlier prevalence of 16.3 per cent reported in 2001-2005. Interpretation & conclusions: Our review shows that overweight and obesity rates in children and adolescents are increasing not just among the higher socio-economic groups but also in the lower income groups where underweight still remains a major concern.

Comparison Among Methods of Retinopathy Assessment (CAMRA) Study: Smartphone, Nonmydriatic, and Mydriatic Photography

PURPOSE We compared smartphone fundus photography, nonmydriatic fundus photography, and 7-field mydriatic fundus photography for their abilities to detect and grade diabetic retinopathy (DR). DESIGN This was a prospective, comparative study of 3 photography modalities. PARTICIPANTS Diabetic patients (n = 300) were recruited at the ophthalmology clinic of a tertiary diabetes care center in Chennai, India. METHODS Patients underwent photography by all 3 modalities, and photographs were evaluated by 2 retina specialists. MAIN OUTCOME MEASURES The sensitivity and specificity in the detection of DR for both smartphone and nonmydriatic photography were determined by comparison with the standard method, 7-field mydriatic fundus photography. RESULTS The sensitivity and specificity of smartphone fundus photography, compared with 7-field mydriatic fundus photography, for the detection of any DR were 50% (95% confidence interval [CI], 43-56) and 94% (95% CI, 92-97), respectively, and of nonmydriatic fundus photography were 81% (95% CI, 75-86) and 94% (95% CI, 92-96%), respectively. The sensitivity and specificity of smartphone fundus photography for the detection of vision-threatening DR were 59% (95% CI, 46-72) and 100% (95% CI, 99-100), respectively, and of nonmydriatic fundus photography were 54% (95% CI, 40-67) and 99% (95% CI, 98-100), respectively. CONCLUSIONS Smartphone and nonmydriatic fundus photography are each able to detect DR and sight-threatening disease. However, the nonmydriatic camera is more sensitive at detecting DR than the smartphone. At this time, the benefits of the smartphone (connectivity, portability, and reduced cost) are not offset by the lack of sufficient sensitivity for detection of DR in most clinical circumstances.

Prevalence of Glucose Intolerance Among Children and Adolescents in Urban South India (ORANGE-2)

AIM This study was designed to determine the prevalence of glucose intolerance (prediabetes or diabetes) in children and adolescents in urban South India. SUBJECTS AND METHODS Children (6-11 years old) and adolescents (12-19 years old) (n=1,519; 777 boys and 742 girls) were randomly selected from residential apartments representing the 10 corporation zones of Chennai city. Height, weight, waist circumference, body fat percentage, and blood pressure were measured using standardized techniques. Investigations included oral glucose tolerance test (OGTT), lipid profile, and fasting insulin. Insulin resistance (IR) was assessed by homeostasis model assessment (HOMA-IR). RESULTS The overall prevalence of glucose intolerance was 3.7% but was higher in girls compared with boys (4.2% vs. 3.2%, P<0.001) and increased to 12.7% in girls with abdominal obesity. On univariate regression, the following risk factors showed significant association with glucose intolerance in girls: adolescent age group (odds ratio [OR] 2.94; confidence interval (CI) 1.12, 7.76), waist circumference (OR 4.45; CI 1.95, 10.14), body mass index (OR 2.73; CI 1.32, 5.65), acanthosis nigricans (OR 2.35; CI 1.14, 4.83), family history of diabetes (OR 2.52; CI 1.07, 5.92), and HOMA-IR (OR 9.30; CI 3.59, 24.12). On multivariate analysis, only family history of diabetes (OR 4.11; CI 1.28, 13.22; P=0.018) and HOMA-IR (OR 11.22; CI 4.19, 30.05; P<0.001) remained significant. In boys only HOMA-IR (OR 5.19; CI 1.54, 17.44; P=0.008) was associated with glucose intolerance. CONCLUSIONS The prevalence of glucose intolerance is high in Asian Indian adolescents, particularly in girls with abdominal obesity.

Relationship of betatrophin with youth onset type 2 diabetes among Asian Indians

BACKGROUND AND AIMS Betatrophin is emerging as a marker for compensatory beta cell proliferation. While betatrophin has been mainly investigated in adults, there is a lack of data on betatrophin levels in youth-onset type 2 diabetes mellitus (T2DM-Y). The aim of this study was to determine levels of betatrophin and its association with T2DM-Y in Asian Indian participants. METHODS We recruited 100 individuals with normal glucose tolerance (NGT; n=50) and newly-diagnosed cases (within 18 months of first diagnosis) of T2DM-Y (n=50) with onset between 12 and 24 years of age from a large tertiary diabetes center in Chennai in southern India. Insulin resistance was measured by homeostatic model (HOMA-IR) and insulin secretion by oral disposition index (DIO). Betatrophin levels were measured by enzyme-linked immunosorbent assay. RESULTS Betatrophin levels were significantly lower in the T2DM-Y group compared with the NGT group (803 vs 1104 pg/ml, p<0.001). Betatrophin showed a significant inverse correlation with waist circumference (p=0.035), HOMA-IR (p<0.001), fasting and 2 h postprandial glucose (p<0.01), glycated hemoglobin (p=0.019) and a positive correlation with fasting C-peptide (p<0.001) and DIO (p=0.012). In regression analysis, betatrophin was independently associated with T2DM-Y even after adjustment for age, gender, and waist circumference (OR per standard deviation: 0.562, 95% CI: 0.342-0.899, p=0.019). However, the association was lost when HOMA-IR was included in the model (OR: 1.141, 95% CI: 0.574-2.249; p=0.646). CONCLUSION Betatrophin levels are lower in T2DM-Y and this association is likely mediated through insulin resistance.