Dalip Ragoobirsingh

The Jamaican Diabetes Survey: A protocol for the Caribbean

OBJECTIVE This study was designed to investigate the point prevalence of diabetes in Jamaica. RESEARCH DESIGN AND METHODS A two-stage stratified random sampling design was used, and individuals aged 15 years and over were interviewed. Nonresponse was documented and factored into the final analysis of the survey data. The overall response rate obtained was 57.9%. All subjects with fasting blood glucose (FBG) > 6.1 mmol/1 (110 mg/dl) were brought back for an abbreviated glucose tolerance test. The data was analyzed using Epi 5, an advanced statistical program designed specifically for use with epidemiological data. RESULTS The 2,109 subjects who participated were the basis for estimates of diabetes and IGT prevalence. Among those with previously diagnosed diabetes, diet therapy alone, oral hypoglycemic agents plus diet therapy, insulin therapy, and lack of treatment were reported. CONCLUSIONS By the World Health Organization (WHO) criteria, Jamaica has a point prevalence of diabetes of 17.9% in the 15-and-over age-group.

Decreased insulin binding to mononuclear leucocytes and erythrocytes from dogs after S-Nitroso-N-Acetypenicillamine administration

BackgroundNitric oxide (NO) and oxygen free-radicals play an important part in the destruction of beta-cells in auto- immune diabetes although the precise mechanism of interaction is still not known. This study was designed to examine any possible diabetogenic effect of NO by investigating any differences in cellular binding of insulin to its receptor on the cell membranes of erythrocytes and mononuclear leucocytes of dogs treated with the NO donor, S-nitroso-N-acetylpenicillamine (SNAP) and controls treated with captopril.ResultsThe result obtained showed decreased binding of insulin to its receptor on the cell membranes of erythrocytes and mononuclear leucocytes. Mononuclear leucocytes from SNAP-treated dogs had decreased ability to bind insulin (16.30 ± 1.24 %) when compared to mononuclear leucocytes from captopril-treated controls (20.30 ± 1.93 %). Similar results were obtained for erythrocytes from dogs treated with SNAP (27.20 ± 1.33 %) compared with dogs treated with captopril (34.70 ± 3.58 %). Scatchard analysis demonstrated that this decrease in insulin binding was accounted for by a decrease in insulin receptor sites per cell, with mononuclear leucocytes of SNAP-treated dogs having 55 % less insulin receptor sites per cell compared with those of captopril-treated controls (P < 0.05). Average affinity and kinetic analysis revealed a 35 % decrease in the average receptor affinity, with mononuclear leucocytes from captopril-treated controls having an empty site affinity of 12.36 ± 1.12 × 10-8 M-1 compared with 9.64 ± 0.11 × 10-8 M-1 in SNAP-treated dogs (P < 0.05).ConclusionThese results suggest that acute alteration of the insulin receptor on the membranes of mononuclear leucocytes and erythrocytes occurred in dogs treated with S-nitroso-N-acetylpenicillamine. These findings suggest the first evidence of the novel role of NO as a modulator of insulin binding and the involvement of NO in the aetiology of diabetes mellitus.

Lipid profile of type 2 diabetic and hypertensive patients in the Jamaican population

Aims: Previous studies have shown that diabetes mellitus (DM) increases the risk of cardiovascular diseases in females to a greater extent than in males. In this cross-sectional study, we evaluated the lipid profiles of type 2 diabetic males and females. Materials and Methods: The study included 107 type 2 diabetic patients (41 males and 66 females), and 122 hypertensive type 2 diabetic patients (39 males and 83 females), aged 15 years and older. Total cholesterol (TC), triglycerides (TG), low density lipoprotein-cholesterol (LDL-C), very low density lipoprotein-cholesterol (VLDL-C) and high density lipoprotein-cholesterol (HDL-C) concentrations were assayed for each group using standard biochemical methods. Results: The mean TC, TG, VLDL-C, HDL-C and LDL-C concentrations, TG/HDL and LDL/HDL ratios were higher in type 2 diabetic and hypertensive type 2 diabetic patients compared with non-diabetic, and hypertensive non-diabetic control subjects, although these were not significant (P > 0.05). Hypertensive type 2 diabetic females had significantly higher serum TC (7.42 ± 1.63 mmol/L) than hypertensive non-diabetic males (5.76±1.57 mmol/L; P < 0.05). All the other lipid and lipoprotein parameters except HDL-C were non-significantly higher in females with type 2 DM and those with hypertension and type 2 DM, compared with type 2 diabetic and hypertensive type 2 diabetic males, respectively (P > 0.05). Conclusion: This study demonstrated that dyslipidemia exists in our type 2 diabetic population with greater TC in hypertensive type 2 diabetic females compared with hypertensive type 2 diabetic males. This suggests that hypertensive type 2 diabetic females are exposed more profoundly to risk factors including atherogenic dyslipidemia compared with males.

A preliminary report on an assessment of a community-based intervention for diabetes control in adults with type 2 diabetes

OBJECTIVE The aim of this study was to evaluate the effectiveness of lay diabetes facilitators (LDFs) to increase knowledge and improve control among persons with diabetes. Methodology. A prospective cohort study was conducted among persons with diabetes in 16 health care centres in Jamaica to evaluate the effect of LDFs on glycaemia [haemoglobin A1c (HbA1c)] and body mass index (BMI). One hundred and fifty-nine persons with diabetes were recruited for the intervention from eight clinical settings in which LDFs had been recruited and trained. A matched group of 159 were recruited as a comparison sample from eight clinical settings without LDFs. HbA1c and BMI were measured at baseline and 6 months. RESULTS Mean HbA1c at baseline for the intervention and comparison groups were 7.9% and 8%, respectively. After 6 months, the intervention group showed a mean decrease of 0.6% while the comparison group showed an increase of 0.6%, significant after control for potential confounders (P < 0.05). There was no statistically significant change in BMI between groups. CONCLUSION Patients educated by LDFs showed improved metabolic control over the first 6 months of observation.

Modulation of glucose uptake in adipose tissue by nitric oxide-generating compounds.

There is increasing evidence that endogenous nitric oxide (NO) influences adipogenesis, lipolysis and insulin-stimulated glucose uptake. We investigated the effect of NO released from S-nitrosoglutathione (GSNO) and S-nitroso N-acetylpenicillamine (SNAP) on basal and insulin-stimulated glucose uptake in adipocytes of normoglycaemic and streptozotocin (STZ)-induced diabetic rats. GSNO and SNAP at 0.2, 0.5, and 1 mM brought about a concentration-dependent increase in basal and insulin-stimulated 2-deoxyglucose uptake in adipocytes of normoglycaemic and STZ-induced diabetic rats. SNAP at 1.0 mM significantly elevated basal 2-deoxyglucose uptake (115.8 ± 10.4%) compared with GSNO at the same concentration (116.1 ± 9.4%;P 0.05) in STZ-induced diabetic rats. Conversely, SNAP at concentrations of 10 mM and 20 mM significantly decreased basal 2-deoxyglucose uptake by 50.0 ± 4.5% and 61.5 ± 7.2% respectively in adipocytes of STZ-induced diabetic rats (P 0.05). GSNO at concentrations of 10 mM and 20 mM also significantly decreased basal 2-deoxyglucose uptake by 50.8 ± 6.4% and 55.2 ± 7.8% respectively in adipocytes of STZ-induced diabetic rats (P 0.05). These observations indicate that NO released from GSNO and SNAP at 1 mM or less stimulates basal and insulin-stimulated glucose uptake, and at concentrations of 10 mM and 20 mM inhibits basal glucose uptake. The additive effect of GSNO or SNAP, and insulin observed in this study could be due to different mechanisms and warrants further investigation.

Acute impairment of insulin signalling by dexamethasone in primary cultured rat skeletal myocytes

In this study, we examined the cellular content of the insulin receptor substrate (IRS)-1, the levels of phosphorylated tyrosine (pY) and serine (pS) residues in IRS-1, and the glucose transporters GLUT-1 and GLUT-4 in primary cultured rat skeletal myocytes treated with the glucocorticoid, dexamethasone. Dexamethasone markedly increased basal and insulin-stimulated IRS-1 content 4 to 5-fold (p < 0.01). A similar level of increase was observed for IRS-1 pY content. However, dexamethasone treatment had no effect on IRS-1 pS content. Further, dexamethasone reduced the cellular content of GLUT-1 when insulin and glucose were absent (p < 0.05), but did not significantly affect the expression of GLUT-4 in the presence of insulin (p > 0.05). We conclude that dexamethasone treatment impairs insulin signalling by a mechanism independent of serine-phosphorylation-mediated IRS-1 depletion, or of impairment of GLUT-1 expression. Instead, dexamethasone-induced insulin resistance may be mediated via reduced cellular content of IRS-1 accompanied by parallel reduction in tyrosine phosphorylation in IRS-1.

Obesity in the Caribbean: the Jamaican experience.

Aim:  This study was designed to investigate the point prevalence and pattern of obesity in the Jamaican adult population.

A cross-sectional study of Jamaican adolescents' risk for type 2 diabetes and cardiovascular diseases.

Objectives To compare obese versus non-obese Jamaican adolescents’ risk for type 2 diabetes (T2D) and cardiovascular diseases (CVDs); and to explore a suitable and economical method of screening for these risk factors in the school settings. Design A descriptive cross-sectional study of adolescents’ risk for T2D and CVD. All the participants were examined at their respective schools. Setting Jamaica, West Indies. Population 276 Jamaican adolescents aged 14–19 years, randomly selected from grades 9 to 12 from 10 high schools on the island and included both boys and girls. All ethnicities on the island were represented. Main outcome measures High fasting blood glucose, total cholesterol, glycated haemoglobin (HbA1c), blood pressure, body mass index (BMI), waist circumference, waist-to-hip ratio, family history of obesity, T2D and CVDs, low physical activity, and presence of Acanthosis Nigricans. All blood measures were analysed using the finger prick procedure. Results Waist circumference, waist-to-hip ratio, Acanthosis Nigricans, total cholesterol, family history of T2D and blood pressure were the strongest predictors of BMI (p=0.001). Over one-third of the participants were overweight. Jamaican adolescent females had a significantly higher number of risk factors and were less physically active than males (p<0.05). Over 80% of participants reported ≥3 risk factors for T2D and CVD. Participants with BMI ≥25 reported five or more risk factors. One-third of the overweight participants were classified with metabolic syndrome. Conclusions Jamaican adolescents are at risk of T2D and CVD. Family history of disease and anthropometric measures identified more participants at risk than did the blood measures. Jamaican adolescent females reported more risk factors for T2D and CVD as compared to males. Collection of this type of data was feasible within the school settings. All data were collected in 1 day per school. Intervention measures are needed to educate Jamaican adolescents to reduce overweight and subsequently the risk factors.

Dyslipidaemia in hypertensive obese type 2 diabetic patients in Jamaica

Introduction Hypertension and obesity are common problems among diabetic patients accelerating progression of vascular diabetic complications. Materials and methods A two-stage stratified random sampling design was used, and individuals aged 15 years and over were interviewed. This cross-sectional study evaluated lipid abnormalities of 117 obese type 2 diabetic patients (28 males and 89 females), and 56 hypertensive obese type 2 diabetic patients (22 males and 34 females). Total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), very-low-density lipoprotein cholesterol (VLDL-C) and high-density lipoprotein cholesterol (HDL-C) concentrations were assayed using standard biochemical methods. Results Hypertensive obese type 2 diabetic females had significantly higher mean serum concentrations of TC (p = 0.043), TG (p = 0.046), LDL-C (p= 0.040), TC/HDL-C ratio (p = 0.001) and LDL-C/HDL-C ratio (p = 0.003) compared with hypertensive obese non-diabetic females. Similar results were found in hypertensive obese type 2 diabetic males compared with hypertensive obese non-diabetic males. Hypertensive obese type 2 diabetic females had significantly higher serum TC, TG and TC/HDL-C ratio (p < 0.05) than hypertensive obese type 2 diabetic males. Hypertensive obese type 2 diabetic females had significantly higher mean serum concentrations of TG (p = 0.03) and TC (p = 0.01) than obese type 2 diabetic females. There was a significant association between blood glucose and LDL-C concentrations in type 2 diabetic subjects (r = 0.36; p< 0.05). Conclusion Obese hypertensive type 2 diabetic females are exposed more profoundly to risk factors including atherogenic dyslipidaemia compared with males.

Nitric oxide agents impair insulin-mediated signal transduction in rat skeletal muscle

BackgroundEvidence demonstrates that exogenously administered nitric oxide (NO) can induce insulin resistance in skeletal muscle. We have investigated the modulatory effects of two NO donors, S-nitroso-N-acetyl-D, L-penicillamine (SNAP) and S-nitrosoglutathione (GSNO) on the early events in insulin signaling in rat skeletal myocytes.ResultsSkeletal muscle cells from 6–8 week old Sprague-Dawley rats were treated with SNAP or GSNO (25 ng/ml) in the presence or absence of glucose (25 mM) and insulin (100 nM). Cellular insulin receptor-β levels and tyrosine phosphorylation in IRS-1 were significantly reduced, while serine phosphorylation in IRS-1 was significantly increased in these cells, when compared to the insulin-stimulated control. Reversal to near normal levels was achieved using the NO scavenger, 2-(4-carboxyphenyl)-4, 4, 5, 5-tetramethylimidazoline-1-oxyl 3-oxide (carboxy-PTIO).ConclusionThese data suggest that NO is a potent modulator of insulin-mediated signal transduction and may play a significant role in the pathogenesis of type 2 diabetes mellitus.