Understanding the predictive accuracy of the InsuTAG index over other surrogate indices in normoglycaemic, non-obese males from Southern India.

We aimed to evaluate the predictive accuracy of InsuTAG index against M value of the hyperinsulinaemic-Euglycaemic clamp (HEC) procedure and fasting surrogate indices of insulin sensitivity/resistance in young, normoglycaemic, Asian Indian males. HEC studies were done in young (mean age 19.7 ± 1 years), non-obese (mean BMI 19.2 ± 2.6 kg/m2), normoglycemic Asian Indian males (n = 110) and the M value was calculated. Surrogate indices namely InsuTAG index, HOMA-IR, FG-IR, QUICKI and McAuley index were calculated. Pearson's correlation and ROC-AUC at 95% CI were applied. Significant negative correlation was observed for InsuTAG index with the M value (r - 0.23, p = 0.01), McAuley index (r - 0.65, p < 0.01), QUICKI (r - 0.34, p < 0.01) and FGIR (r - 0.35, p < 0.01). Significant positive correlations of InsuTAG index were observed for BMI and waist circumference. The ROC-AUC was higher for InsuTAG index (0.75) than FGIR (0.30), QUICKI (0.31), and McAuley index (0.20). The InsuTAG cut-off value ≥ 19.13 showed 66.7% sensitivity and 69.2% specificity in this study group.

Comprehensive evaluation of patterns of hypoglycemia unawareness (HUA) and glycemic variability (GV) in patients with fibrocalculous pancreatic diabetes (FCPD): A cross-sectional study from South India.

OBJECTIVES: Hypoglycemia unawareness (HUA) in patients with FCPD is common with an unclear etiology. We evaluated the prevalence, characteristics of HUA, glycemic variability (GV), its possible association with pancreatic glucagon secretion & cardiac autonomic function in patients with FCPD. METHODS: A two-week ambulatory glucose profile (AGP) and cardiac autonomic function test was done in patients with FCPD (n = 60), and categorized into UNAWARE (n = 44) and AWARE (n = 16) groups based on the Hypoglycemia Unawareness Index (HUI) score. Glycaemic variability was assessed from the AGP data using Easy GV 9.0.2 software. A subset of patients from both the groups (n = 11) underwent a mixed-meal challenge test and were compared with healthy individuals (controls; n = 11). RESULTS: HUA was evidenced in 73% (44/60) of patients with FCPD. Significant hypoglycemia, nocturnal hypoglycemia, duration of hypoglycemia and poor cardiac autonomic functions (p = 0.01) were prominent in the UNAWARE group. The overall GV was greater in the UNAWARE group. In the UNAWARE group, significantly reduced fasting and post prandial glucagon levels negatively correlated with HUI (r = -0.74, p < 0.05) and GV-hypoglycemia indices (p < 0.05) In contrast, significantly higher post prandial glucagon levels in the AWARE group positively correlated with post prandial hyperglycemia (r = 0.61, p < 0.05). CONCLUSION: Heterogeneity in patterns of glucagon secretion were significantly associated with HUA and GV. Reduced glucagon levels contribute to greater risks of HUA, nocturnal hypoglycemia and greater GV, while hyperglucagonemia predisposes to postprandial hyperglycemia and hypoglycemia awareness in patients with FCPD.

An Atypical Form of Diabetes Among Individuals With Low BMI.

OBJECTIVE: Diabetes among individuals with low BMI (<19 kg/m2) has been recognized for >60 years as a prevalent entity in low- and middle-income countries (LMICs) and was formally classified as "malnutrition-related diabetes mellitus" by the World Health Organization (WHO) in 1985. Since the WHO withdrew this category in 1999, our objective was to define the metabolic characteristics of these individuals to establish that this is a distinct form of diabetes. RESEARCH DESIGN AND METHODS: State-of-the-art metabolic studies were used to characterize Indian individuals with "low BMI diabetes" (LD) in whom all known forms of diabetes were excluded by immunogenetic analysis. They were compared with demographically matched groups: a group with type 1 diabetes (T1D), a group with type 2 diabetes (T2D), and a group without diabetes. Insulin secretion was assessed by C-peptide deconvolution. Hepatic and peripheral insulin sensitivity were analyzed with stepped hyperinsulinemic-euglycemic pancreatic clamp studies. Hepatic and myocellular lipid contents were assessed with 1H-nuclear magnetic resonance spectroscopy. RESULTS: The total insulin secretory response was lower in the LD group in comparison with the lean group without diabetes and the T2D group. Endogenous glucose production was significantly lower in the LD group than the T2D group (mean ± SEM 0.50 ± 0.1 vs. 0.84 ± 0.1 mg/kg · min, respectively; P < 0.05). Glucose uptake was significantly higher in the LD group in comparison with the T2D group (10.1 ± 0.7 vs. 4.2 ± 0.5 mg/kg · min; P < 0.001). Visceral adipose tissue and hepatocellular lipids were significantly lower in LD than in T2D. CONCLUSIONS: These studies are the first to demonstrate that LD individuals in LMICs have a unique metabolic profile, suggesting that this is a distinct entity that warrants further investigation.

Exocrine pancreatic insufficiency related fat malabsorption and its association with autonomic neuropathy in Asian Indians with type 2 diabetes mellitus.

BACKGROUND AND AIMS: We aimed to estimate the prevalence of exocrine pancreatic insufficiency (EPI) related fat malabsorption & to correlate it with measures of autonomic neuropathy in patients with T2DM from India. METHODS: Patients with T2DM (cases; n = 118) and normo-glycaemic individuals (controls; n = 82) underwent anthropometry and biochemical evaluation at baseline. The 72-hours fecal fat excretion was estimated by the Van de Kamer's titration method. Autonomic neuropathy was evaluated using an automated analyzer. RESULTS: The prevalence of EPI related fat malabsorption in cases was 45% (n = 53; 72 hours mean fecal fat level = 22.7 ± 5.6 g/day). Dysfunctions in the parasympathetic nervous system (PNS; 86.7%; p < 0.05), sympathetic nervous system (SNS; 92.4%; p < 0.05), and both; PNS + SNS (83.1%; p < 0.05) were significant. Amongst measures of PNS dysfunction, there was a significantly higher percentage of abnormal expiration: inspiration ratio (45.3%) and the 30:15 ratio (84.9%) (p < 0.05) in patients with T2DM and EPI related fat malabsorption. CONCLUSION: In this cross-sectional cohort of Asian Indian patients with T2DM (n = 118), EPI related fat malabsorption correlates significantly with autonomic dysfunction in patients with T2DM. However, these preliminary data need to confirmed in trials with more robust design.

Significance of single and multi-voxel 1H magnetic resonance spectroscopy in the quantification of myocellular lipid in young non-obese Asian Indian males.

To prospectively assess intramyocellular lipids (IMCL) and extramyocellular lipids (EMCL) using single voxel spectroscopy (SVS) and multi voxel magnetic resonance spectroscopy (MVS) in soleus muscle and correlate results with metabolic variables in non-obese (BMI < 23 kg/m2) Asian Indian males. Thirty one patients with diabetes (cases) and twelve normoglycaemic subjects (controls) underwent point resolved spectroscopy sequence (PRESS) of soleus muscle using SVS and MVS in a 3 T MRI scanner. Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were measured from MRI images and body composition was measured from dual-energy x-ray absorptiometry (DXA). The mean IMCL from SVS and MVS were 1.6% and 2.6% in cases and 2.3% and 3.4% in controls respectively. The mean EMCL from SVS and MVS were 1.8% and 3% in cases and 1.5% and 3% respectively in controls. A significant correlation between IMCL and total fat mass (rho = 0.42, p < 0.01) and total body fat (rho = 0.46; p < 0.01) were observed in cases while using the SVS technique and no correlations were found in the MVS technique. The SVS showed significant correlations between total myocellular lipids with VAT and SAT in cases alone. Total myocellular lipids acquired using both techniques showed a significant correlation with BMI, waist circumference, total fat mass, total body fat and truncal fat in cases alone. Quantification of IMCL of soleus muscle using the SVS technique is useful in studying the relationship with metabolic markers in non-obese Asian Indians with diabetes.

The triglyceride/glucose ratio is a reliable index of fasting insulin resistance: Observations from hyperinsulinaemic-euglycaemic clamp studies in young, normoglycaemic males from southern India.

BACKGROUND & AIMS: Non-obese Asians have a high propensity to develop insulin resistance. Therefore, screening such individuals for insulin resistance using simple surrogate indices is important. In this study, we aimed to validate the triglyceride-glucose (Tg/glu) ratio against the M value of hyperinsulinaemic-euglycaemic clamp (HEC) procedure and other surrogate indices of insulin resistance in normoglycaemic Indian males from Southern India. METHODS: A cohort of 105 normoglycaemic males (mean BMI: 19.2 ± 2.6 kg/m2) underwent HEC procedure. Surrogate indices of insulin resistance viz. the triglyceride-glucose (Tg/Glu) ratio, the triglyceride-glucose index, the McAuley's index, the HOMA-IR, the QUICKI, the fasting glucose to insulin ratio (FG-IR), and the fasting C- peptide index were calculated and correlated with the M value. The cut-off value for the Tg/Glu ratio was obtained using the Receiver Operator Characteristics (ROC) with Area under curve (AUC) analysis at 95% confidence interval (CI). The P value < 0.05 was considered statistically significant. RESULTS: The Tg/Glu ratio demonstrated significantly higher AUC (0.81), when compared to the Tg × glu index (0.63), 20/fasting C peptide × fasting plasma glucose index (0.55), HOMA-IR (0.47), QUICKI (0.26), FGIR (0.12) and McAuley's index (0.18). For the Tg/Glu ratio, a cut-off value ≥ 1.19 had high sensitivity (80%) and specificity (79%) values (PPV: 16%; NPV: 98.8%) respectively. CONCLUSION: The Tg/Glu ratio can be used as a reliable surrogate index to screen for risk of insulin resistance in lean, normoglycaemic males from Southern India.