The Unitarian Hypothesis for the aetiology of diabetes mellitus.

Over the years, several clinical syndromes have been described in diabetes mellitus. Although world opinion has settled somewhat on the main two types, the debate continues as to how the 'formes frustes' syndromes fit in and what if any implications there are for the accepted aetiology of the disease. Type 1, insulin dependent diabetes mellitus, results from pancreatic inadequacy as a result of a variety of insults such as autoimmune attack, toxic damage, etc. Insulin administration is at the core of the therapeutic approach. Type 2, non insulin dependent diabetes mellitus, results from reduced responsiveness of the target tissues to insulin and as such, an insulin resistance syndrome is described. Lifestyle adjustment and oral hypoglycaemic agents are the mainstay of therapy. Over the years, however, insulin insufficiency will develop in most cases and insulin therapy required in order to achieve normoglycaemia. The aetiology of these main two types has been maintained to be distinct from each other and as such types 1 and 2 are described as two separate developmental conditions. Furthermore, the variant patterns, such as malnutrition related, drug induced, intermittent or phasic insulin requiring, gestational, temporary, stress related, etc., all present a challenge as to how they fit in aetiologically. The Unitarian Hypothesis, by presenting this overall cascade of biochemical and physiological interactions, brings a logic which embraces the points of entry of a variety of insults, all of which can lead to the clinical picture of hyperglycaemia and its attendant adverse outcomes. The hypothesis buttresses the belief that nature - the genetic predisposition which directs potential antibody development; and nurture - the environmental influences such as nutritional status (over- or under-), infective and toxic attack, can aggravate or initiate aspects of the cascade of reactions leading to hyperglycaemia. The causative agents functioning internally within the cascade are imputed to be free radicals, oxidizing molecular species and antibodies and the corollary to this overview concept would be that a situation that minimizes the genesis and accumulation of these three agents would minimize the development of diabetes mellitus. Currently the debate is rife about the use of free radical scavengers and antioxidants in the treatment and prevention of diabetes mellitus. The verdict is still out on this approach. Our research on rootcrops such as yams and cassava, staple foods in tropical countries, indicates the presence of cyanoglycosides such as linamarin, which on digestion yields cyanide radicals. These radicals are pancreatotoxic especially in the undernourished state. Dog models however, have shown that free radical scavengers such as riboflavin, Vitamin B(2), is protective against this toxic damage. Further, scientific investigations have clearly demonstrated the role of antibody attack and have been able to ward off the appearance of type 1 diabetes mellitus in susceptible individuals, by the early use of immunosuppressive therapy such as cyclosporin. Thus the Unitarian Hypothesis demonstrates how all types of clinical syndromes being described in diabetes mellitus are not necessarily variants of a specific illness but rather manifestations of a central process of membrane damage-->antibody response-->insulin inadequacy (quantitatively or qualitatively); and the future intervention in containing this disease may well lie in focusing on preservation of the integrity of the body's cell membranes.

The effect of annatto on insulin binding properties in the dog.

Various plants are used in Caribbean folklore for the treatment of a variety of illnesses including diabetes mellitus. Preliminary investigations of several crude plant extracts have indicated that the annatto (Bixa orellana), among others, does in fact exhibit hypoglycaemic properties. This present investigation sought to isolate the hypoglycaemic principle(s) from the crude extract and to determine the mechanism of action. Purification experiments employing thin layer chromatography (TLC) and high performance liquid chromatography (HPLC) resulted in an oil-soluble, partially purified annatto extract. The latter caused a decrease in blood glucose level of 5.62+/-0.13 (n=34) mmol/dL versus 6.31+/-0.12 (n=34) for the control (p<0.01) 1 h after administration. This hypoglycaemia persisted for an additional hour when the oral glucose tolerance test (OGTT) was performed on dogs treated with annatto and compared with the control. Plasma insulin levels measured at 1.0 h showed that there was an increase in plasma insulin levels of 59.57+/-8.3 microIU/mL for the annatto treated dogs versus 40.95+/-5.46 microIU/mL for the control (p<0.05), this elevation persisted throughout the duration of the OGTT which followed. Insulin receptor studies, using a modification of the method of Gambhir et al. done on mononuclear leucocytes and erythrocytes obtained from blood taken 1 h after administration showed that there was an increase in the percentage receptor binding when compared with the control. Insulin affinity results showed that there was an increase of 1.8+/-0.2x10(8) m-1 (n=12) in mononuclear leucocytes for the annatto treated dogs versus 1.2+/-0.2x10(8) m-1 for the control (p<0.05). In the enythrocytes, there was also an increase in affinity from 1.2+/-0.2x10(8) m-1 to 2.3+/-0.2x10(8) m-1 for the control and treated animals, respectively. In conclusion, it can be stated that annatto is responsible for the hypoglycaemic episodes seen in the dogs which was mediated by an increase in plasma insulin concentration as well as an increase in insulin binding on the insulin receptor due to elevated affinity of the ligand for the receptor.

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. METHODS: A two-stage-stratified random sampling design was used, and individuals aged 15 years and over were interviewed. In addition, anthropometric measurements were performed. The data were analysed using the SPSS statistical software version 8. Non-response was documented and factored into the final analysis of the survey data. RESULTS: A total of 2105 individuals responded to the all island survey, with 69% being females. Truncal obesity and gynoid obesity showed similar prevalence data. Both were affected by increasing age, being female, level of education attained and smoking status. CONCLUSIONS: Jamaica has a point prevalence of obesity, truncal 36.2% and gynoid 34.1%, in the 15 and over age group.

The effect of capsaicin on blood glucose, plasma insulin levels and insulin binding in dog models.

Capsicum frutescens has been used to treat diabetes mellitus by traditional healers in Jamaica. This study was designed to identify any hypoglycaemic principle(s) and to determine the mechanism of action. Purification experiments employing thin layer chromatography (TLC) and high performance liquid chromatography (HPLC) led to the extraction of the active principle, capsaicin. Capsaicin caused a decrease in blood glucose levels of 4.91 +/- 0.52 (n = 6) mmol/dL versus 6.40 +/- 0.13 mmol/dL (n = 6) for the control (p < 0.05) at the 2.5 h time interval when the oral glucose tolerance test (OGTT) was performed on dogs treated with capsaicin and compared with the control. Plasma insulin levels measured at the 2.5 h time interval showed that there was an increase in plasma insulin levels of 5.78 +/- 0.76 microIU/mL (n = 6) for the capsaicin treated dogs versus 3.70 +/- 0.43 microIU/mL (n = 10) for the control (p < 0.05). Insulin receptor studies, using a modification of the method of Gambhir et al. done on monocytes obtained from blood at the 2.5 h time interval showed that there was a decrease in the percentage receptor binding for the capsaicin treated dogs when compared with the control. Insulin affinity results showed that there was a decrease of 2.4 x 10(-4) in monocytes for the capsaicin treated dogs versus 8.77 x 10(-4) for the control (p < 0.05). Also, insulin receptor calculations showed a decrease in number, 2.63 x 10(8) +/- 5.73 x 10(7), compared with 8.77 x 10(8) +/- 1.47 x 10(8) for the control. In conclusion it can be stated that capsaicin is responsible for the hypoglycaemic episodes seen in the dogs and that it also causes an increase in insulin secretion which leads to a reduction of insulin binding on the insulin receptors.

Effects of S-nitroso-N-acetyl-penicillamine administration on glucose tolerance and plasma levels of insulin and glucagon in the dog.

It has been suggested that nitric oxide (NO, nitrogen monoxide) is a regulator of carbohydrate metabolism in skeletal muscle. The present study was undertaken to investigate the acute effects of the nitric oxide donor S-nitroso-N-acetylpenicillamine (SNAP) on blood glucose levels and on the gluco-regulatory hormones insulin and glucagon in healthy dogs. The acute effects of SNAP on mean arterial pressure and heart rate were also investigated. The drug was administered intravenously and the pre- and postprandial blood glucose, plasma insulin, and glucagon concentrations were determined at half-hour time intervals postadministration after a glucose challenge. The plasma nitrate and nitrite concentrations were measured and taken as the biochemical markers of in vivo NO formation. The oral glucose tolerance test revealed an impaired glucose tolerance in SNAP-treated dogs as reflected by the area under the glucose curve, 1150.50 +/- 63.00 mmol x 150 min and 1355.25 +/- 102.01 mmol/L x 150 min in dogs treated with 10 and 20 mg/kg of SNAP, respectively, compared with 860.25 +/- 60.68 mmol/L x 150 min in captopril-treated controls (P < 0.05). The 2-h blood glucose concentration in dogs treated with 20 mg/kg body wt of SNAP was 9.17 +/- 1.10 mmol/L compared with 5.59 +/- 0.26 mmol/L for captopril-treated controls (P = 0.015). The oral glucose tolerance test also confirmed an impaired insulin secretion in the SNAP-treated dogs. While the plasma insulin concentration increased gradually in the captopril-treated controls to a peak value of 39.50 +/- 2.55 microIU/ml, 1.5 h after a glucose challenge there was a decrease in the plasma insulin concentration in SNAP-treated dogs to a low value of 20.67 +/- 0.88 microIU/ml (P = 0.006). In contrast, there were no significant differences in plasma glucagon concentration in SNAP-treated dogs and captopril-treated dogs at any time points. Using the Griess reaction, we found that there was a 27-95% increase in plasma nitrate/nitrite concentration on administration of SNAP. The sustained hyperglycemic effect observed in SNAP-treated dogs was accompanied by a marginal decrease in the mean arterial blood pressure and a significant increase in heart rate (P < 0.05). We conclude that acute administration of SNAP in the oral glucose tolerance test releases NO that modulates the parameters of carbohydrate metabolism.

The hyperglycemic effect of S-nitrosoglutathione in the dog.

The present study investigates the pharmacological activity of the nitric oxide (NO) donor S-nitrosoglutathione (GSNO) on the plasma glucose and insulin levels in healthy normoglycemic dogs. The plasma nitrate and nitrite concentrations were measured by a commercial autoanalyzer and taken as the biochemical markers of in vivo nitric oxide formation. Plasma glucose levels were measured by the glucose oxidase method, while the insulin levels were determined by radioimmunoassay. The possible effect of the coadministration of ascorbic acid (vitamin C) and GSNO on plasma glucose levels was also examined. In healthy normoglycemic dogs, administration of 35 and 50 mg/kg of GSNO caused a dose-dependent increase in postprandial plasma glucose levels. The plasma glucose levels were significantly elevated at the 1.5-, 2.0-, and 2.5-h time intervals of the oral glucose tolerance test at both concentrations of GSNO (P < 0.05). These values were significantly higher than those obtained using captopril (control). Furthermore, coadministration of 35 mg/kg of GSNO and 50 mg/kg ascorbic acid enhanced the postprandial hyperglycaemic effect observed for the administration of only 35 mg/kg of GSNO. There was a 35-100% increase in plasma nitrate concentration on administration of both doses of GSNO. Intravenous administration of GSNO (35 mg/kg) and captopril (20 mg/kg) significantly decreased the mean arterial blood pressure and increased the heart rate. The blood pressure-lowering effect of these drugs was more pronounced on systolic than on diastolic blood pressure (P < 0.05). These results suggests that in healthy normoglycaemic dogs: (a) nitric oxide released from GSNO increases postprandial plasma glucose levels and inhibits glucose-stimulated insulin secretion, (b) ascorbic acid enhances the postprandial hyperglycaemic effect of GSNO, probably by increasing the release of NO, and (c) GSNO decreases mean arterial blood pressure and increase heart rate in normotensive dogs.

Kidney function in phasic insulin dependent diabetes mellitus in Jamaica.

In Jamaica, malnutrition related diabetes mellitus (MRDM) presents the clinical picture of phasic insulin dependence. This study was undertaken to investigate nephropathic changes associated with this group of patients. Fourteen phasic insulin dependent diabetes mellitus (PIDDM) patients were compared with 10 insulin dependent (IDDM) and 10 non-insulin dependent (NIDDM) diabetes mellitus patients, and 10 normal controls. Each group was matched for age, sex, body mass index (BMI) and, in the case of the diabetic patient controls, duration of diabetes. Urinary microalbumin concentration was significantly (p < 0.05) higher in the PIDDM group (mean +/- SD: 153 +/- 48.3 mg/dl) than in the groups of NIDDM (35.7 +/- 9.6 mg/dl) or IDDM (38.6 +/- 15.8 mg/dl) patients. Serum urea and creatinine concentrations (mean +/- SE 7.6 +/- 1.0 mmol/l and 130.0 +/- 20.3 mumol/l, respectively) were higher in the PIDDM patients than in the NIDDM and IDDM groups. Confounding factors such as hypertension and urinary tract infections were excluded as causes for these differences. We conclude that PIDDM patients have more severe renal dysfunction than NIDDM patients and, since glycosylated haemoglobin concentrations are comparable in these groups, we attribute this to a renal insult due to malnutrition predating the onset of the PIDDM.

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) greater than 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.

Change in serum cholinesterase activity in Jamaican diabetics.

This study investigates the alteration of serum cholinesterase levels in diabetics and its possible relationship to blood glucose, insulin, triglyceride, and cholesterol levels. Fourteen phasic insulin-dependent diabetes mellitus patients were compared with 10 insulin-dependent diabetes mellitus, 10 noninsulin-dependent diabetes mellitus, and 10 normal controls. Each group was matched for age, sex, body mass index, and duration of diabetes. Mean age was 56.7 +/- 2.5 years; mean body mass index, 24.0 +/- 0.8 kg/m2; and mean duration of diabetes, 14.2 +/- 2.2 years. Serum acetylcholinesterase, insulin, triglyceride, and cholesterol levels as well as fasting blood sugar were all assayed using standard techniques. Results suggest an associated increase of serum acetylcholinesterase with triglyceride levels in diabetics and may point to a possible association between increased serum acetylcholinesterase and vascular complications in Jamaican diabetics.

J type diabetes revisited.

J type diabetes is grouped as a subtype of type III or malnutrition-related diabetes, known as protein-deficient pancreatic diabetes, (PDPD). J type diabetes has not been reported recently, but a clinical picture called phasic insulin-dependent diabetes mellitus (PIDDM) has been elaborated in Jamaica, the same home country of PDRD and appears to be a "formes frustes" syndrome. The following comparative studies were performed on a group of diabetic patients and normal controls: insulin receptor binding; renal, hepatic, and pancreatic function; and abdominal ultrasonography. The results show a considerably decreased white and red blood cell binding to insulin (P less than .05), extensive kidney damage (P less than .05), and increased pancreatic echogenicity in PIDDM, supporting a separate identity of this latter syndrome from types I and II diabetes mellitus. Also, the features of relative insulin resistance, absence of ketosis even in the presence of severe hyperglycemia, and intermittent insulin requirement suggests that PIDDM, J type diabetes, and PDPD are one and the same syndrome.

Radiological evaluation of the pancreas in malnutrition-related (phasic insulin dependent) diabetes mellitus.

This study was undertaken to investigate pancreatic changes associated with phasic insulin dependent diabetes mellitus (PIDDM). Twelve PIDDM patients were studied. They were compared with groups of patients, 10 insulin dependent (IDDM), 10 non-insulin dependent (NIDDM), and 10 normal controls. Each group was matched for age, sex, and body mass index. For the study, the mean age was 56.7 +/- 2.5 years, mean body mass index 24.0 +/- 0.8, and mean duration of diabetes 14.2 +/- 2.2 years. Flat abdominal radiograph and ultrasonography were performed on each participant. The results suggest an increased echogenicity of the pancreas in the phasic insulin dependent group of patients.

Insulin receptor studies of erythrocytes and mononuclear leucocytes in phasic insulin diabetes mellitus.

This study was designed to investigate any differences in cellular binding of insulin between phasic insulin-dependent (malnutrition-related) diabetes mellitus (PIDDM) and insulin-dependent, non-insulin-dependent, and normal controls. Isolated, washed red and white blood cells obtained after 12-14 hr fast, were separately incubated with varying concentrations of non-radioactive insulin, and a fixed quantity of radioactively labelled insulin. After the 3-hr incubation, cells were washed with buffer, and radioactivity determined on an autogamma counter. Percentage binding, receptor sites number and affinity were all determined by linear regression of the Scatchard plot. Fasting plasma insulin and glucose levels were also assayed. The results obtained show decreased binding of insulin in red blood cells [11.3 +/- 1.3%) and white blood cells 2.9 +/- 0.5%) in PIDDM. This was due to decreased receptor sites (red blood cells 39 +/- 11; white blood cells 0.5 +/- 0.11 x 10(4] as well as decreased affinity (red blood cells 0.14 +/- 0.03 x 10(9) M-1; white blood cells 0.17 +/- 0.04 x 10(9) M-1) when compared to the normal and diabetic (both insulin and non-insulin-dependent) controls. Phasic insulin-dependent diabetes (malnutrition-related diabetes mellitus) is characterized by decreased red and white cellular binding to insulin, in addition to decreased production of insulin.

Insulin receptor studies of erythrocytes and mononuclear leucocytes in phasic insulin diabetes mellitus

This study was designed to investigate any diferences in cellular binding of insulin between phasic insulin-dependent (malnutrition-related) diabetes mellitus (PIDDM) and insulin-dependent, non-insulin-dependent, and normal controls. Isolated, washed red and white blood cells obtained after 12 - 14hr fast, were separately incubated with varying concentrations of non-radioactive insulin, and a fixed quantity of radioactively labellede insulin. After the 3hr incubation, cells were washed with buffer, and radioactivity determined on an autogamma counter. Percentage binding, receptor sites number and affinity were all determined by linear regression of the Scathard plot. Fasting plasma insulin and glucose levels were were also assayed. The results obtained showed decreased binding of insulin in red blood cells (11.3+or -1.3%) and white blood cells 2.9 + or -o.5%) in PIDDM. This was due to decreased receptor sites (red blood cells 39+ or -11; white blood cells 0.5+ or -0.11x 10 to the 4th) as well as decreased affinity (red blood cells 0.14+ or -0.03 x 10 to the 9th M-1; white blood cells 0.17 + or -0.04 x10 to the 9th M-1) when compared to the normal and diabetic (both insulin and non-insulin-dependent) controls. Phasic insulin-dependent diabetes (malnutition-related diabetes mellitus) is characterized by decreased red and white cellular binding to insiulin, in addition to decreased production of insulin

Effect of alcohol on serum lipids in diabetics.

This report emanated from a three-year study conducted at the Diabetic Outpatient Clinics convened at the Port-of-Spain and Sangre-Grande Hospitals in Trinidad. The diabetic population which participated consisted of 132 men and 245 women of African descent; and 99 men and 163 women of East Indian origin. The mean age was 50 years (+/- 13). The effect of alcohol on lipid fractions varied in the two races. A lower incidence of ischaemic heart disease was observed among the alcohol consumers when compared to those who abstained.

Effect of alcohol on serum lipids in diabetics

This report emanated from a three-year study conducted at the Diabetic Outpatient Clinics convened at the Port-of-Spain and Sangre-Grande Hospitals in Trinidad. The diabetic population which participated consisted of 132 men and 245 women of African descent; and 99 men and 163 women of East Indian origin. The mean age was 50 years (ñ13). The effect of alcohol on lipid fractions varied in the races. A lower incidence of ischaemic heart disease was observed among the alcohol consumers when compared to those who abstained

The effect of blood sugar, therapy and blood pressure on lipoprotein profiles of diabetics in Trinidad & Tobago. Possible association with ischaemic heart disease.

The aim of this investigation was to examine the effects of fasting blood sugar, the type of therapy and blood pressure levels on lipoprotein profiles of diabetics in Trinidad and Tobago, and to determine how these biochemical and physiological risk factors may influence the development of ischaemic heart disease. Seven hundred (700) diabetic patients attending outpatient clinics at Sangre Grande and Port-of-Spain General Hospitals were surveyed. The data obtained in this study on the relationship of serum lipids to diabetic control support the hypothesis that poor control of blood sugar is conducive to accelerated atherosclerosis. Hypertensive patients and those maintained on insulin showed a greater predisposition to ischaemic heart disease (IHD) than did non-hypertensives and patients maintained on oral hypoglycaemic agents, respectively.

The effect of demographic factors on serum lipids in diabetics of Trinidad and Tobago. Possible association with ischaemic heart disease.

This study was undertaken in order to investigate the effect of race, sex, weight, activity level and residential area on serum lipoprotein patterns, and to determine how this could possibly relate to the incidence of ischaemic heart disease (IHD). Seven hundred (700) diabetics attending outpatient clinics at Sangre-Grande and Port-of-Spain hospitals were screened. There were 132 males and 249 females of African descent; 99 males and 163 females of East Indian extract, and 19 males and 38 females of other ethnic origins. The average age of the population studied was 50 years (+/- 15). The results obtained from this study indicate that diabetes mellitus is apparently more common in women that in men, particularly in those women who have borne children, and the incidence rises markedly after menopause. East Indians have higher triglyceride (TG), very low density lipoprotein cholesterol (VLDL-C) and low density lipoprotein cholesterol (LDL-C), but lower high density lipoprotein cholesterol (HDL-C) concentrations than their counterparts of African origin. TG, LDL-C and total serum cholesterol (TC) concentrations are highest in overweight-obese patients while HDL-C concentrations are highest in the lower weight division. The domestic working class, as well as those who were in retirement, have higher TG, LDL-C and TC than members of other occupational status. The fractions mainly affected by a residential area are TG, HDL-C and LDL-C. Moreover, diabetes mellitus and its consequent impact on lipoprotein homeostasis imposes a greater predilection to IHD, especially among members of the East Indian community.

The effect of demographic factors on serum lipids in diabetics of Trinida & Tobago: possible association with ischaemic ischamic heart disease

This study was undertaken in order to investigate the effect of race, sex, weight, activity level and to determine how this could possibly relate to the incidence of ischaemic heart disease (IHD). Seven hundred (700) diabetics attending outpatient clinics at Sangre-Grande and Port-of-Spain hospitals were screened. There were 132 males and 249 females of African descent; 99 males and 163 females of East Indian extract, and 19 males and 38 females of other ethnic origins. The average age of the population studied was 50 years (ñ 15). The results obtained from this study indicate that diabetes mellitus is apparently more common in women that in men, particularly in those women who have borne children, and the incidence rises markedly after menopause. East Indians have higher triglyceride (TG), very low density lipoprotein cholesterol (VLDL-C) and low density lipprotein cholesterol (LDL-C), but lower high density liprotein cholesterol (HDL-c) concentrations than their counterparts of African origin. TG, LDL-C and total serum cholesterol (TC) concentrations are highest in overweight-obese patients while HDL-C concentrations are highester in the lower weight division. The domestic working class, as well as those who were in retirement, have higher TG, LDL-C than members of ther occupational status. The fractions mainly affected by a residental area are TG, HDL-C. Moreover, diabetes mellitus and its consequent impact on lipoprotein homeostasis a greater predilection to IHD, especially among members of the East Indian community

The relationship between different lipoprotein fractions and the incidence of coronary heart disease in diabetics of Trinidad & Tobago.

This study was undertaken in order to investigate the relationship between the different lipoprotein fractions and the incidence of coronary heart disease (CHD) in diabetics of Trinidad and Tobago. Seven hundred (700) diabetics attending outpatient clinics at Sangre-Grande and Port-of-Spain hospitals were screened. There were 132 males and 249 females of African descent; 99 males and 163 females of East Indian extraction and 19 males and 38 females of other ethnic origins. The average age of the population studied was 50 years (+/- 15). From this survey, it is evident that the impact of the diabetic state on lipoprotein homeostasis results in elevation of serum lipid concentrations. The elevation of low density lipoprotein cholesterol seems to be the most reliable lipid risk indicator of the lipoprotein profile, predisposing patients to a coronary event. The data also provides unequivocal evidence that diabetic patients of Trinidad and Tobago have more coronary atherosclerosis and a higher incidence of clinical CHD than does the non-diabetic population of similar age.