Diabetes distress in a Barbadian population with type 2 diabetes: A pilot test.

One in five Barbadians has diabetes, suggesting that there is a severe burden of the disease. Objective: To assess the psychometric properties of the Diabetes Distress Scale, in order to determine the feasibility, practicality, internal consistency and criterion validity of the instrument when used with Barbadians living with Type 2 Diabetes. Methods: Patients with type 2 diabetes, (n = 106. 60% females, 40% males; mean age = 65.2, 11.3 years) attending a private clinic in Barbados were assessed for diabetes distress, depression, glycated hemoglobin (HbA1C) and blood pressure (BP).A self-report questionnaire that included: clinical and demographic questions; the Diabetes Distress Scale (DDS); the Patient Health Questionnaire (PHQ-9); and the Problem Areas In Diabetes (PAID-5) scale. Glycated haemaglobin (HbA1C) and Blood pressure (BP) were also measured. Results: Of the 110 persons who participated, 106 persons completed the questionnaire. The Cronbach alpha coefficient of the PAID was 0.92 and the DDS was 0.92. Concurrent validity was demonstrated in a strong consistent relationship between the scores on the DDS and PAID-5, with a strong positive correlation, r = 0.70, n = 86, p < 0.001. There was a significant difference in the DDS scores between males (M = 1.26, SD = 0.37) and females (M = 1.50, SD = 0.73), t(73.31) = -1.99, p = 0.05 two tailed. Conclusion: The DDS is shown to be a valid and reliable measure within this Caribbean context. Thus, researchers and clinicians desirous of a tool to assess Diabetes Distress may be assured of the strong psychometric properties demonstrated thus far.

Diabetes distress in Barbadian adults with type 2 diabetes.

Purpose: Psychological disorders such as diabetes distress may negatively influence how patients effectively manage their illness. Therefore, discernment of such influential psychosocial components could be pertinent in promoting competent diabetes management. The vital psychosocial aspect of diabetes distress in diabetes management within the Caribbean context remains unexplored. The purpose of this study therefore was to investigate the prevalence and distribution of diabetes distress (DD), and explore its relationship to socio-demographic and clinical characteristics in Barbadian adults with type 2 diabetes(T2DM). Methods: A cross-sectional survey was conducted with adults (n = 509) ages 20-80 years with T2DM. The survey comprised, a profile section, and a standardized questionnaire-the Diabetes Distress Scale (DDS). In addition, biological (A1C and blood pressure measurements were also collected. Results: The sample comprised 30.8% males and 69.2% females. Moderate to high DD identified in 17% of the patients (9.4% moderate distress, 7.2% high distress). Moderate distress was more frequent in unmarried persons; younger persons had high DD. There was no difference in rates of moderate to high DD in women (16.7%) compared to men (16.2%) and, as age and years lived with diabetes increased, diabetes distress decreased. Conclusions: The results emphasized the need for considerations that must be given to Barbadian diabetes patients' mental well-being. In recognition of the role DD plays in the patients' experiences, screening should be incorporated into clinical care.

Self-care adherence and affective disorders in Barbadian adults with type 2 diabetes.

PURPOSE: Diabetes management requires adherence to complicated self-care behaviors. Therefore, the emotional state of the individual living with diabetes, is likely to affect their ability to comply with recommendations. This study explored the relationship of self-care adherence to diabetes distress and depression in Barbadian adults with type 2 diabetes. METHODS: Adults aged 20 to 80 years, with type 2 diabetes, completed self-report questionnaires comprised of a profile section consisting of demographic and clinical characteristics; and standardized questionnaires comprising, The Diabetes Distress Scale (DDS), The Patient Health Questionnaire (PQH-9), and the Summary of Diabetes Self-care Activities Scale (SDSCA). Additionally biological measures (BP and HbA1c) were collected. RESULTS: For the 509 participants there were no differences in adherence for males (30.8%) and females (69.2%), high diabetes distress and depression were associated with low adherence. General diet was negatively associated with BP and HbA1c; while HbA1c was positively correlated with blood glucose testing. CONCLUSION: Self-care non-adherence is more than a behavioral problem; it is a multidimensional phenomenon inclusive of demographic factors, condition or disease factors, psychological and social factors.

Depression in Barbadian adults with type 2 diabetes.

PURPOSE: The aim of this study was to explore the frequency and distribution of depression in Barbadian adults with type 2 diabetes. METHODS: Adults aged 20-80 years with type 2 diabetes, completed a cross-sectional survey comprised of, a profile section, and the standardized questionnaire; the Patient Health Questionnaire (PHQ-9). Additionally, biological (HbA1c and blood pressure) measurements were collected. RESULTS: For the 509 participants, 65.4%, 1.4%, 22% and 8% showed minimal, moderately severe to severe; mild and moderate depression respectively. Female participants ranked higher in depression than males. Persons who reported having never been married were identified as having the greatest prevalence of mild and severe depression. There was a small positive correlation between glycemic control and depression. CONCLUSIONS: The results suggest that the presence of this affective disorder may be under-recognized in Barbadian patients with type 2 diabetes mellitus. Management protocol could incorporate the screening for depression.

Decreased Prevalence of Diabetes Mellitus in Jamaica.

The purpose of this paper is to report the dramatic changes in the point prevalence of diabetes mellitus in the adult population of Jamaica following education intervention. The initial prevalence in the 15-and-over age group was determined by a two-stage stratified random sampling design in 1993. In 1997, the University of the West Indies Diabetes Outreach Project thru its public service arm, the Diabetes Association of Jamaica, developed and implemented a Peer Facilitators Diabetes Education Programme. This effort has realized an increased patient and public education as well as concomitant increased patient compliance and a reduction in related complications. The Jamaica Health and Lifestyle Survey 2008 examined, using a stratified, random, two-stage cluster sample survey, and a nationally representative sample of 2848 Jamaicans aged 15-74. The most dramatic outcome is the decrease in the prevalence from 17.9% to 7.9% in the adult population, age 15+.

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.

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.

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.

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 comparison of the new international diabetes federation definition of metabolic syndrome to WHO and NCEP definitions in Chinese, European and South Asian origin adults.

OBJECTIVES: To compare the prevalence, agreement and phenotypic characteristics in three ethnic groups of the new International Diabetes Federation (IDF) definition of metabolic syndrome (MS) to the World Health Organization (WHO) and national cholesterol education program (NCEP) definitions. SETTING: Newcastle upon Tyne, England. DESIGN: Cross-sectional surveys. PARTICIPANTS: Chinese (171 men and 185 women), European (257 men and 301 women), and South Asian (264 men and 295 women) adults, ages 25 to 64 years. MAIN OUTCOME MEASURES: Anthropometric indices: blood pressure, fasting lipids, urine albumin-to-creatinine ratio, glucose intolerance, insulin resistance. RESULTS: IDF-defined MS was highly prevalent in all groups, ranging from 12.3% (95% CIs 7.4-17.2) in Chinese men to 45.5% (39.5-51.5) in South Asian men. In women, of all ethnic groups, more than 80% of those with WHO- or NCEP-defined MS also had IDF-defined MS. In men, however, agreement was less good. For example, in each ethnic group, more than a third of those with WHO-defined MS did not have IDF-defined MS. Within each ethnic group, the biological characteristics of those with MS by any definition were largely the same. However, differences existed between ethnic groups. For example, in those with IDF-defined MS, both South Asian men and women had significantly (P < .05) higher insulin resistance and significantly lower systolic and diastolic blood pressure than Europeans or Chinese. CONCLUSIONS: Agreement between the IDF and other definitions is better in women than men. The phenotype is similar within each ethnic group whatever the definition, but differs between groups suggesting that risks associated with MS differ by ethnic group.

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.

Increased PC-1 phosphodiesterase activity and inhibition of glucose uptake in adipocytes of type 2 diabetic rats.

This study was designed to understand the cellular mechanisms responsible for defects in the insulin-stimulated signal transduction pathway in a type 2 diabetic animal model. We examined the in vitro PC-1 phosphodiesterase activity and glucose uptake in adipose tissue of streptozotocin (STZ)-induced type 2 diabetic rats. The PC-1 activity was significantly increased in adipose tissue of diabetic rats (0.54 +/- 0.08 nmol PNTP hydrolyzed/mg protein/min) compared with controls (0.29 +/- 0.05 nmol PNTP hydrolyzed/mg protein/min, p < 0.05). Upon insulin stimulation (100 nM), glucose uptake in the adipose tissue of the controls (4.17 +/- 1.28 x 10(-8) micromol/mg/min) was significantly higher than that in the diabetic rats (1.26 +/- 0.35 x 10(-8); p < 0.05). These results suggest that elevated PC-1 phosphodiesterase activity and decreased glucose uptake in adipose tissues may be acquired characteristics contributing to the development of type 2 diabetes mellitus.

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 less than 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 less than 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 less than 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.

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

BACKGROUND: Evidence 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. RESULTS: Skeletal 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-beta 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). CONCLUSION: These 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.

Exogenous nitric oxide inhibits IRS-1 expression in rat hepatocytes and skeletal myocytes.

Accumulative evidence has supported the role of nitric oxide (NO) in a variety of normal physiological functions as well as many pathological conditions. In this study, we examined the possible diabetogenicity of NO by measuring the expression of the insulin receptor substrate (IRS)-1 in rat hepatocytes and skeletal myocytes. IRS-1 is important in the insulin-mediated signal transduction pathway in both liver and skeletal muscle. Exogenous NO donated by S-nitroso-N-acetylpenicillamine (SNAP) and S-nitrosoglutathione (GSNO) resulted in significant reduction in levels of IRS-1 in both cells, when compared to the insulin-stimulated control (p<0.001). 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). SNAP was the more potent drug, and the skeletal myocytes were the more sensitive cells to the inhibitory effects of NO released from the drugs. These results provide further evidence that exogenous NO is a potent modulator of insulin-mediated signal transduction and may play a significant role in the pathogenesis of type 2 diabetes mellitus.

Acute effects of exogenous nitric oxide on glucose uptake in skeletal muscle of normoglycaemic and diabetic rats.

BACKGROUND: The role of nitric oxide (NO) in the modulation of basal and insulin-stimulated glucose uptake remains controversial. The aim of this study was to investigate the role of NO released from its donors, S-nitrosoglutathione (GSNO) and S-nitroso-N-acetylpenicillamine (SNAP), on glucose uptake in skeletal muscle of normoglyceamic and type 2 diabetic rats. MATERIAL/METHODS: Skeletal muscle strips of type 2 diabetic and normoglycaemic Sprague-Dawley rats were incubated with or without various concentrations (200 microM, 500 microM, 1000 microM, 10 mM & 20 mM) of SNAP or GSNO in the presence or absence of insulin (100 nM or 10 microM). The associated radioactivity was determined by liquid scintillation counting in a Beckman LS6000 scintillation counter programmed for dual-channel counting. RESULTS: SNAP and GSNO at 1000 microM significantly elevated basal and insulin-stimulated 2-deoxyglucose uptake (P<0.05) in normoglycaemic and diabetic rats. Millimolar concentrations (10 & 20 mM) of GSNO and SNAP significantly decreased basal and insulin-stimulated glucose uptake in skeletal muscle strips of normoglycaemic and type 2 diabetic rats in a concentration-dependent manner (P<0.05). The inhibition of insulin-stimulated glucose uptake was greater in the diabetic rats using both NO donors compared with normoglycaemic rats (P<0.05). CONCLUSIONS: The stimulatory effect of micromolar concentrations of GSNO and SNAP enhances basal and insulin-stimulated glucose uptake in normoglycaemic and type 2 diabetic rats, however higher concentrations elicited an inhibitory effect in normoglycaemic and diabetic rats. This highlights the NO-glucose uptake mechanism as a possible potential therapeutic target in the treatment of type 2 diabetes.

The effect of nitric oxide on glucose metabolism.

Nitric oxide (NO) is an important bioactive signaling molecule that mediates a variety of normal physiological functions, which, if altered, could contribute to the genesis of many pathological conditions, including diabetes. In this study, we examined the possible diabetogenicity of NO by noting differences in the cellular binding of insulin in dogs treated with the NO donor, S-nitrosoglutathione (GSNO) compared to captopril-treated controls. GSNO administration resulted in an abnormality in glucose metabolism which was attributed to decreased binding of insulin to its receptor on the cell membrane of mononuclear leucocytes, 11.60 +/- 0.60% in GSNO-treated dogs compared with 18.10 +/- 1.90% in captopril-treated control (p < 0.05). The decreased insulin binding was attributed to decreased insulin receptor sites per cell, 21.43 +/- 2.51 x 10(4) in GSNO-treated dogs compared with 26.60 +/- 1.57 x 10(4) in captopril-treated controls (p < 0.05). Average affinity analysis of the binding data demonstrated that this decrease in insulin binding was also due to a decrease in average affinity of the receptor on mononuclear leucocytes for insulin. This was evident by a decrease in empty and filled site affinities in GSNO-treated dogs compared with that of captopril-treated dogs (p < 0.05). It appears that GSNO is exerting its effect by decreasing the number of insulin receptor sites and/or decreasing the average receptor affinity. These results provide evidence for a novel role of NO as a modulator of insulin binding and the involvement of NO in the aetiology of diabetes mellitus.

Isolation and purification of the hypoglycaemic principle present in Capsicum frutescens.

Capsicum frutescens has been used to treat diabetes mellitus by traditional healers in Jamaica. Purification experiments employing thin layer chromatography (TLC) and high performance liquid chromatography led to the extraction of the active principle, capsaicin. Purified capsaicin caused a decrease in blood glucose levels to 4.91 +/- 0.52 (n = 6) mmol/dL versus 6.40 +/- 0.13 mmol/dL (n = 6) for the control (p < 0.05) at 2.5 h in an OGTT in dogs. There was a concomitant elevation in plasma insulin levels (p < 0.05). In conclusion, it can be stated that capsaicin is the major constituent of Capsicum frutescens that is responsible for the hypoglycaemic episodes seen in the dogs. It is also apparent that the latter is mediated by insulin release.

The effect of nitric oxide on glucose metabolism.

Nitric oxide (NO) is an important bioactive signaling molecule that mediates a variety of normal physiological functions, which, if altered, could contribute to the genesis of many pathological conditions, including diabetes. In this study, we examined the possible diabetogenicity of NO by noting differences in the cellular binding of insulin in dogs treated with the NO donor, S-nitrosoglutathione (GSNO) compared to captopril-treated controls. GSNO administration resulted in an abnormality in glucose metabolism which was attributed to decreased binding of insulin to its receptor on the cell membrane of mononuclear leucocytes, 11.60 ± 0.60% in GSNO-treated dogs compared with 18.10 ± 1.90% in captopril-treated control (p < 0.05). The decreased insulin binding was attributed to decreased insulin receptor sites per cell, 21.43 ± 2.51 × 10(4) in GSNO-treated dogs compared with 26.60 ± 1.57 × 10(4) in captopril-treated controls (p < 0.05). Average affinity analysis of the binding data demonstrated that this decrease in insulin binding was also due to a decrease in average affinity of the receptor on mononuclear leucocytes for insulin. This was evident by a decrease in empty and filled site affinities in GSNO-treated dogs compared with that of captopril-treated dogs (p < 0.05). It appears that GSNO is exerting its effect by decreasing the number of insulin receptor sites and/or decreasing the average receptor affinity. These results provide evidence for a novel role of NO as a modulator of insulin binding and the involvement of NO in the aetiology of diabetes mellitus. (Mol Cell Biochem 263: 29-34, 2004).