Immunomodulation by helminths: Similar impact on type 1 and type 2 diabetes?

The incidence of both type 1 (T1D) and type 2 diabetes (T2D) is drastically increasing, and it is predicted that the global prevalence of diabetes will reach almost 600 million cases by 2035. Even though the pathogenesis of both types of diabetes is distinct, the immune system is actively involved in both forms of the disease. Genetic and environmental factors determine the risk to develop T1D. On the other hand, sedentary life style, surplus of food intake and other lifestyle changes contribute to the increase of T2D incidence. Improved sanitation with high-quality medical treatment is such an environmental factor that has led to a continuous reduction of infectious diseases including helminth infections over the past decades. Recently, a growing body of evidence has implicated a negative association between helminth infections and diabetes in humans as well as animal models. In this review, we discuss studies that have provided evidence for the beneficial impact of helminth infections on T1D and T2D. Possible mechanisms are presented by which helminths prevent T1D onset by mitigating pancreatic inflammation and confer protection against T2D by improving insulin sensitivity, alleviating inflammation, augmenting browning of adipose tissue and improving lipid metabolism and insulin signalling.

Association of adiposity, measured by skinfold thickness, with parental history of diabetes in a South Indian population: data from CURES-114.

PURPOSE OF THE STUDY: To look at the association of central and peripheral skinfold thickness with parental history of diabetes in subjects without diabetes. METHODS: Subjects with no parental history of diabetes (n=1132), subjects with one parent with diabetes (n=271) and subjects with both parents with diabetes (n=51) were recruited from the Chennai Urban Rural Epidemiological Study (CURES) conducted between 2001 and 2003. Biceps, triceps, medial calf, mid-thigh, chest, abdomen, mid-axillary, suprailiac and subscapsular sites were measured with Lange skinfold callipers. RESULTS: Trunk fat measurements, such as chest (p=0.020), mid-axillary (p=0.005), suprailiac (p=0.014), subscapsular (p<0.001) and abdomen (p=0.010) skinfolds, were highest in subjects with both parents with diabetes followed by those with one parent with diabetes, and lowest in those with no parental history of diabetes. However, the peripheral fat measurements, ie, biceps, triceps, medial calf and mid-thigh, were not significantly different between the study groups. Total truncal and peripheral fat skinfold thicknesses showed a significant positive association with other indices of obesity such as body mass index (BMI) and waist circumference in relation to trunk fat (BMI: r=0.748, p<0.001; waist: r=0.776, p<0.001) and peripheral fat (BMI: r=0.681, p<0.001; waist: r=0.569, p<0.001). CONCLUSIONS: A significant association was observed between truncal and peripheral fat, assessed by skinfold thickness, and parental history of diabetes among subjects without diabetes in this urban South Indian population.

Association of serum adiponectin with diabetic microvascular complications among south Indian type 2 diabetic subjects - (CURES-133).

OBJECTIVES: To assess the association of serum adiponectin and microvascular complications of diabetes in an urban south Indian type 2 diabetic population. DESIGN AND METHODS: Diabetic subjects [n=487] were included from Chennai Urban Rural Epidemiology Study (CURES). Four-field stereo retinal color photography was done and diabetic retinopathy (DR) was classified as non-proliferative DR (NPDR) or proliferative DR (PDR) according to the Early Treatment Diabetic Retinopathy Study grading system. Sight threatening DR (STDR) was defined as the presence of NPDR with diabetic macular edema, and/or PDR. Neuropathy was diagnosed if vibratory perception threshold of the great toe using biothesiometry exceeded ≥20V. Nephropathy was diagnosed if urinary albumin excretion (UAE) was ≥30µg/mg creatinine. Serum total adiponectin levels were measured by radioimmunoassay. RESULTS: Subjects with any microvascular complications had significantly higher levels of adiponectin levels compared to those without the complications (geometric mean: 6.1 vs. 5.3µg/mL, p=0.004). The adiponectin level was significantly higher in subjects with DR (6.8 vs. 5.5µg/mL, p=0.004) and neuropathy (5.6 vs. 6.5µg/mL, p=0.024) compared to those without. Adiponectin levels were not significantly different in subjects with and without nephropathy. Serum adiponectin levels increased with the severity of DR [No DR - 5.5µg/mL; NPDR without DME - 6.5µg/mL; STDR - 8.3µg/mL, p=0.001]. Regression analysis revealed adiponectin to be associated with microvascular disease (presence of neuropathy and/or retinopathy and/or nephropathy) (OR: 1.44, 95% CI: 1.01-2.06, p=0.049) even after adjusting for age, gender, BMI, HbA1c, diabetes of duration, serum cholesterol and triglycerides, hypertension and medication status. CONCLUSION: In Asian Indians with type 2 diabetes, serum adiponectin levels are associated with microvascular complications and also with the severity of retinopathy.

Circulating levels of high molecular weight (HMW) adiponectin and total adiponectin in relation to fat distribution, oxidative stress and inflammation in Asian Indians.

AIM: To look at the association of total and high molecular weight (HMW) adiponectin with markers of fat distribution, oxidative stress and inflammation in Asian Indians. METHODS: A total of 120 subjects were chosen randomly from Chennai Urban Rural Epidemiological Study. Fasting HMW adiponectin levels, TNF-alpha and oxidized LDL were measured using ELISA. High sensitivity C reactive protein (hsCRP) was measured by a high sensitive nephelometric assay. Lipid peroxidation was measured by Tbars assay and protein carbonyl content was assessed by DNPH assay. Visceral and subcutaneous fat areas were assessed by computed tomography (CT) scan. RESULTS: When stratified based on the tertiles of visceral fat, the levels of total (p=0.03) and HMW adiponectin (p=0.007) were highest in the first tertile followed by tertiles 2 and 3 whereas in tertiles of subcutaneous fat, there was no such trend. With increasing tertiles of Tbars, the levels of total (p=0.03) and HMW adiponectin decreased (p=0.002). The levels of HMW (p< 0.001) but not total adiponectin was also found to decrease with increasing tertiles of Protein carbonyl content. The levels of Total (p=0.02) and HMW adiponectin (p=0.004) were highest in the first tertile of oxidized LDL followed by tertile 2 and tertile 3. With increasing tertiles of TNF-alpha total (p=0.01) and HMW adiponectin (p=0.004) was found to decrease. With increasing tertiles of hs-CRP, Total (p=0.005) and HMW adiponectin (p=0.007)was found to decrease. CONCLUSION: Oxidative stress markers, visceral but not subcutaneous fat and inflammation are associated with total and HMW adiponectin levles in Asian Indians.

Association of cystatin-C with metabolic syndrome in normal glucose-tolerant subjects (CURES-97).

BACKGROUND: This study looked at the association of cystatin-C (cys-C) with severity of metabolic syndrome in Asian Indians. METHODS: Five sets of normal glucose tolerance subjects were recruited from the Chennai Urban Rural Epidemiology Study (CURES), a population-based study in southern India: 43 subjects with no metabolic risk factors, 44 subjects with one metabolic risk factor, 37 subjects with two risk factors, 40 subjects with three risk factors, and 40 subjects with four or five metabolic risk factors. Metabolic syndrome was defined using National Cholesterol Education Program criteria for adults modified for waist measured using the World Health Organization Asia Pacific guidelines. Serum cys-C was estimated by a high-sensitivity particle-enhancing nephelometry assay. RESULTS: Subjects with four or five metabolic abnormalities had the highest cys-C levels, and with decreasing number of metabolic abnormalities, the cys-C levels decreased linearly (P for trend < 0.001). Regression analysis showed a linear increase in cys-C levels with increasing number of metabolic abnormalities. CONCLUSION: Cys-C levels are highly correlated with the number of metabolic abnormalities in Asian Indians.

Association of hypoadiponectinemia with non-alcoholic fatty liver disease in urban south Indians--(CURES - 81).

BACKGROUND & OBJECTIVES: Association between adiponectin and non-alcoholic fatty liver disease (NAFLD) has been reported in west. Studies in Indian population are lacking. This study was undertaken to assess the association of hypoadiponectinemia with NAFLD in Asian Indians. METHOD: In this cross-sectional study, subjects were randomly selected from Phase 5 of the Chennai Urban Rural Epidemiology Study (CURES), an epidemiological study based on a representative population of Chennai in south India. One hundred twenty one subjects without NAFLD and 72 subjects with NAFLD were selected. NAFLD was diagnosed by ultrasonography. Serum adiponectin levels were measured using radioimmunoassay. Insulin resistance was calculated using Homeostasis Assessment model (HOMA-IR). RESULTS: Serum adiponectin values were significantly lower in subjects with NAFLD compared to those without [5.6 µg/ml (95% Confidence Interval (CI) 5.0 - 6.3 µg/ml] vs 7.4 µg/ml (95% CI: 6.7 - 8.1 µg/ml, P<0.01). Adiponectin levels decreased with increasing severity of NAFLD. Subjects with moderate to severe steatosis had significantly lower adiponectin levels (5.1µg/ml, 95% CI: 4.1- 6.4 µg/ml) compared to subjects with mild steatosis (5.9 µg/ml, 95% CI: 5.0 - 6.9 µg/ml; P<0.001) and subjects without NAFLD (7.3 µg/ml, 95% CI: 6.6 - 8.0 µg/ml; P<0.01). Multiple logistic regression analysis revealed adiponectin to be negatively associated with NAFLD [Odds Ratio (OR): 0.865, 95% Confidence Interval (CI): 0.792- 0.944, P=0.001]. This remained statistically significant even after adjusting for confounding factors age, gender, body mass index, insulin resistance, waist circumference, total cholesterol, triglycerides and glucose intolerance (OR: 0.873, 95% CI: 0.793 - 0.961; P=0.005). INTERPRETATION & CONCLUSION: NAFLD is associated with lower serum adiponectin levels independent of conventional cardiovascular risk factors in Asian Indians known to have high prevalence of diabetes and coronary artery disease.

Adiponectin and carotid intimal medial thickness in subjects with and without glucose intolerance (CURES-82).

OBJECTIVE: This study assessed the association of serum adiponectin with carotid intimal medial thickness (IMT) in Asian Indians with different grades of glucose intolerance. METHODS: Subjects with normal glucose tolerance (NGT) (n = 520), impaired glucose tolerance (IGT) (n = 115), and type 2 diabetes mellitus (T2DM) (n = 540) were recruited from the Chennai Urban Rural Epidemiology Study, in south India. Adiponectin levels were measured using radioimmunoassay. Carotid IMT was assessed by high resolution B-mode ultrasonography. Insulin resistance was calculated using the homeostasis assessment model. RESULTS: Subjects with glucose intolerance (i.e., IGT and T2DM) were older compared to subjects with NGT. Waist circumference, systolic blood pressure, and serum triglycerides were higher among subjects with IGT and T2DM compared to subjects with NGT (P < 0.001). Subjects with glucose intolerance had significantly higher mean carotid IMT values and lower adiponectin compared to subjects with NGT (P < 0.001). Serum adiponectin levels were significantly correlated with IMT among NGT (P = 0.005) and IGT (P = 0.005) subjects but not in subjects with diabetes. Linear regression analysis revealed adiponectin to be negatively associated with IMT (P < 0.001) even after adjusting for age, gender, body mass index, insulin resistance, and glucose intolerance (P < 0.001). CONCLUSIONS: Carotid IMT is associated with lower serum adiponectin levels independent of conventional cardiovascular risk factors in urban South Indians.