Diabetes in tropical Africa: a prospective study, 1981-7. II. Course and prognosis.

OBJECTIVE--To determine the clinical course of diabetes mellitus in tropical Africa. DESIGN--Continuing care and follow up until 31 March 1989 of all newly diagnosed diabetic patients registered at one hospital between 1 June 1981 and 31 May 1987. SETTING--Muhimbili Medical Centre, Dar es Salaam, Tanzania. SUBJECTS--1250 Newly diagnosed diabetic patients seen over a six year period. 272 (21.8%) Had diabetes requiring insulin, 825 (66.0%) diabetes not requiring insulin, and 153 (12.2%) diabetes of uncertain type. MAIN OUTCOME MEASURES--Survival rates during each year of follow up. RESULTS--205 (16.4%) Patients were known to have died, 126 (61.5%) in hospital and 79 (38.5%) in the community. At least a further 71 patients were likely to have died. The five year survival rates (95% confidence intervals) for patients with diabetes requiring and not requiring insulin were 71% (62% to 80%) and 84% (80% to 89%) respectively for known deaths and 60% (51% to 69%) and 82% (77% to 86%) respectively for known plus probable deaths. 49 (3.9%) Patients died at the time of presentation. Severe diabetic ketoacidosis and infection were responsible for most deaths in patients with diabetes requiring insulin. Infection was responsible for 24% of deaths in patients with diabetes not requiring insulin and was the main cause of death in the group with uncertain type of diabetes. Cardiovascular and renal causes were responsible for 24% of hospital deaths of patients with diabetes not requiring insulin. Diabetes requiring insulin, young age, and ketonuria at presentation were associated with a significantly worse five year survival on multivariate analysis. On univariate analysis underweight, female sex, low educational background, and manual occupations were additional factors with a worse prognosis. CONCLUSION--Diabetes in sub-Saharan Africa is, in many patients, a serious disease with a poor prognosis. Most deaths, however, are due to preventable causes. More effort is therefore required to increase public awareness of diabetes and to improve patient detection, management, and follow up.     

Must diabetes be a fatal disease in Africa? Study of costs of treatment.

OBJECTIVE--To estimate the costs of diagnosis and treatment of diabetes in Tanzania. DESIGN--Costs estimated from the reported and recorded experience of patients with newly presenting diabetes in 1989-90 and of diabetic patients first seen in 1981-2. SETTING--Muhimbili Medical Centre, Dar es Salaam. SUBJECTS--464 patients (315 men and 149 women). 262 patients diagnosed during 1 September 1989-31 August 1990 (group 1) and 202 during 1 June 1981-31 August 1982 (group 2). RESULTS--The average annual direct cost of diabetes care in 1989-90 was $287 for a patient requiring insulin and $103 for a patient not requiring insulin. Purchase of insulin accounted for 68.2% ($156) of the average annual outpatient costs for patients requiring insulin. For patients not requiring insulin the cost of oral hypoglycaemic drugs and treatment of chronic complications and infections accounted for 42.5% ($29.3) and 48.8% ($33.7) of costs respectively. Cost of outpatient care of diabetic patients for the whole of Tanzania was estimated at $2.7m, *75,128 (32.2%) of which was for insulin. Doctors'' and nurses'' costs accounted for 0.2% of total costs of outpatient care. The annual direct inpatient care costs were estimated at $1.25m. Around 0.2% of the Tanzanian population aged 15 years and over used the equivalent of 8% of the total government health expenditure, which was $47,4088,382. CONCLUSION--Diabetes places a severe strain on the limited resources of developing countries. If African patients with diabetes have to pay for their treatment most will be unable to do so and will die.     

Leptin in type 2 diabetic or myotonic dystrophic women.

BACKGROUND: Insulin resistance is an important determinant of circulating leptin concentrations in humans, but its independent contribution on plasma leptin levels are controversial. In the present study, we characterized plasma leptin levels and their regulation in women with 2 different insulin resistance states: type 2 diabetes and myotonic dystrophy disease, and in controls. MATERIAL AND METHODS: We studied 3 groups of women: 21 type 2 diabetic patients, 20 myotonic dystrophic patients and a control group of 20 normoglycemic subjects, matched in age and body mass index. Body composition, fasting glucose and insulin, IGF-I, IGF-binding protein-3 and leptin were studied. Body composition was measured using a bioelectrical impedance analyser. Insulin sensitivity (in percentage) was modeled according to a computer-based homeostasis model assessment model. Data are expressed in mean +/- SEM. RESULTS: In both groups of patients, glucose concentrations were higher in type 2 diabetic patients than in myotonic dystrophic patients, and insulin concentrations and insulin sensitivity were similar in the 2 groups of patients (82.4 +/- 18.6% in type 2 diabetic patients vs. 69.7 +/- 9.7% in myotonic dystrophic patients, p = 0.2) and lower than in controls. Serum leptin and leptin/fat mass ratio were higher in myotonic dystrophic patients than in type 2 diabetic patients (30 +/- 4.9 ng/ml vs. 17.7 +/- 2.6 ng/ml, p = 0.03 and 2.32 +/- 0.69 ng/ml/kg vs. 1.07 +/- 0.2 ng/ml/kg, p = 0.02, respectively) or those found in controls. In type 2 diabetic patients, leptin concentrations were correlated with body mass index and body fat, and in myotonic dystrophic patients leptin concentrations were correlated with age, body mass index, fasting insulin and lower insulin sensitivity, whereas leptin concentrations were not correlated with body fat. CONCLUSIONS: These findings suggest that leptin concentrations and regulation in myotonic dystrophic patients are different from type 2 diabetes.     

Systemic and regional free fatty acid metabolism in type 2 diabetes

To determine whether type 2 diabetes mellitus alters systemic and regional free fatty acid ([3H]palmitate) metabolism, 14 nondiabetic (ND) and 14 type 2 diabetic (D) subjects underwent hyperinsulinemic-hyperglycemic (approximately 9.3 mM) clamps. The subjects were matched for age, body mass index, percent body fat, and fat-free mass. D subjects had more (P < 0.05) visceral fat than ND. During somatostatin, replacement growth hormone, and glucagon infusions, insulin was infused to achieve moderate (approximately 75 pmol/l) and high (approximately 150 pmol/l) physiological insulin levels. D subjects had greater (P < 0.02) systemic and regional (splanchnic and leg) palmitate release than ND subjects during both insulin infusion intervals. The relative contributions of splanchnic, leg, and nonsplanchnic upper body regions to systemic palmitate release did not differ between groups, although the last contributed the most (approximately 75%) to systemic palmitate release. Visceral fat area correlated with systemic palmitate flux (r = 0.45, P < 0.03) during both insulin infusions. We conclude that type 2 diabetes is associated with a generalized impairment in insulin suppression of lipolysis compared with equally obese ND individuals.     

Diabetes in prison: can good diabetic care be achieved?

OBJECTIVE--To investigate the clinical characteristics and metabolic control of diabetic patients given structured diabetic care in prison. DESIGN--Survey of diabetic men serving prison sentences during a 22 month period in a large British prison. SETTING--HM Prison, Walton, Liverpool. SUBJECTS--42 male diabetic prisoners, of whom 23 had insulin dependent and 19 non-insulin dependent diabetes. MAIN OUTCOME MEASURES--Episodes of diabetic instability, glycated haemoglobin concentrations, body mass index. RESULTS--No serious diabetic instability occurred. Between the initial assessment by the visiting consultant diabetologist and a second assessment 10 weeks later glycated haemoglobin concentrations had fallen from 10.8 (SD 2.9)% to 9.8 (2.4)% (p less than 0.05) in prisoners with insulin dependent diabetes and from 8.7 (1.9)% to 7.6 (1.2)% (p less than 0.05) in those with non-insulin dependent diabetes. Good glycaemic control continued, a mean glycated haemoglobin concentration of 7.6 (1.5)% being recorded in seven men remaining in prison for six to 18 months. Mean body mass index (weight (kg)/(height(m))2) did not change during the study (insulin dependent prisoners 23.3 (SD 2.1), non-insulin dependent prisoners 27.9 (3.8)). CONCLUSIONS--Good diabetic metabolic control is usual in prison, probably due to the rigid dietary regimen, no alcohol, and compliance with treatment. Many younger men had defaulted from their home diabetic clinics, and imprisonment allowed screening for diabetic complications and reassessment of treatment. Structured diabetic care should be offered in all prisons.     

Effect of exercise training on insulin sensitivity and glucose metabolism in lean, obese, and diabetic men.

To clarify the impact of vigorous physical training on in vivo insulin action and glucose metabolism independent of the intervening effects of concomitant changes in body weight and composition and residual effects of an acute exercise session, 10 lean, 10 obese, and 6 diet-controlled type II diabetic men trained for 12 wk on a cycle ergometer 4 h/wk at approximately 70% of maximal O2 uptake (VO2max) while body composition and weight were maintained by refeeding the energy expended in each training session. Before and 4-5 days after the last training session, euglycemic hyperinsulinemic (40 mU.m2.min-1) clamps were performed at a plasma glucose of 90 mg/dl, combined with indirect calorimetry. Total insulin-stimulated glucose disposal (M) was corrected for residual hepatic glucose output. Body weight, fat, and fat-free mass (FFM) did not change with training, but cardiorespiratory fitness increased by 27% in all groups. Before and after training, M was lower for the obese (5.33 +/- 0.39 mg.kg FFM-1.min-1 pretraining; 5.33 +/- 0.46 posttraining) than for the lean men (9.07 +/- 0.49 and 8.91 +/- 0.60 mg.kg FFM-1.min-1 for pretraining and posttraining, respectively) and lower for the diabetic (3.86 +/- 0.44 and 3.49 +/- 0.21) than for the obese men (P less than 0.001). Insulin sensitivity was not significantly altered by training in any group, but basal hepatic glucose production was reduced by 22% in the diabetic men. Thus, when intervening effects of the last exercise bout or body composition changes were controlled, exercise training per se leading to increased cardiorespiratory fitness had no independent impact on insulin action and did not improve the insulin resistance in obese or diabetic men.     

Metabolic abnormalities in first-degree relatives of type 2 diabetics

Diabetic relatives and obese subjects are at increased risk for development of diabetes mellitus, and therefore are classed as potential abnormality of glucose tolerance (POT-AGT). Disturbances of lipid and purine metabolisms have been reported in diabetic and obese non-diabetic subjects. In obese subjects above alterations are probably due to hyperinsulinemia. This study aimed at verifying whether similar metabolic abnormalities could be found in relatives of non-insulin dependent diabetic patients and whether they could be related to possible glucose intolerance. We have studied 10706 outpatients and 95 hospitalized subjects, aged between 20 and 50 years. We have selected 4 groups according to diabetic relationship and body mass index: A (normal weight subjects), B (obese subjects), C (normal weight NIDDM-relatives), D (overweight NIDDM-relatives). The NIDDM-relatives showed higher prevalence of hyperglycemia, as expected; furthermore the relatives with normal glucose tolerance had higher glucose area during OGTT. Serum levels of uric acid and insulin response to oral glucose were increased in all obese subjects, but abnormalities of lipid metabolism and fasting hyperinsulinemia were found only in obese NIDDM-relatives. These results suggest that family history of diabetes mellitus can be a risk for metabolic disturbance even in absence of glucose intolerance. Furthermore some metabolic disorders observed in obese subjects could be due to an associated and not sufficiently investigated family history of diabetes.     

Relationship between plasma leptin and zinc levels and the effect of insulin and oxidative stress on leptin levels in obese diabetic patients

Leptin is thought to be a lipostatic signal that contributes to body weight regulation. Zinc plays an important role in appetite regulation also. Our aim is to evaluate the relationship between leptin and zinc in obese and nonobese type 2 diabetic patients and its relationship with oxidative stress and insulin. We studied 25 nonobese nondiabetic women (controls); 35 nonobese diabetic women; and 45 obese diabetic women. Plasma leptin concentration was determined by immunoradiometric assay. Thiobarbituric acid reactive substances (TBARS), markers of oxidative stress, were assayed by the spectrofotometric method. Plasma levels of zinc and insulin were measured by atomic absorption spectrophotometer and electrochemiluminescence methods, respectively. We found that nonobese diabetic patients had significantly lower zinc and higher TBARS levels than control subjects (P<0.01). There was no difference in plasma leptin levels between nonobese diabetic subjects and controls. Obese diabetic subjects had significantly higher plasma leptin, TBARS, and insulin levels and significantly lower plasma zinc levels than nonobese diabetic subjects (for each comparison; P<0.01). The univariate and multivariate analyses demonstrated a significant positive correlation between leptin and body mass index (P<0.01) and insulin (P<0.01), and a significant negative correlation between leptin and zinc in obese subjects. Additionally, TBARS levels was positive correlated with insulin and negative correlated with zinc in obese diabetic subjects. We conclude that zinc may be a mediator of the effects of leptin, although the detailed mechanism is still unknown and requires further investigation. Free radical induced mechanism(s) may be involved in this process.     

Influence of PPAR-alpha agonist fenofibrate on insulin sensitivity and selected adipose tissue-derived hormones in obese women with type 2 diabetes

PPAR-alpha agonists improve insulin sensitivity in rodent models of obesity/insulin resistance, but their effects on insulin sensitivity in humans are less clear. We measured insulin sensitivity by hyperinsulinemic-isoglycemic clamp in 10 obese females with type 2 diabetes before and after three months of treatment with PPAR-alpha agonist fenofibrate and studied the possible role of the changes in endocrine function of adipose tissue in the metabolic effects of fenofibrate. At baseline, body mass index, serum glucose, triglycerides, glycated hemoglobin and atherogenic index were significantly elevated in obese women with type 2 diabetes, while serum HDL cholesterol and adiponectin concentrations were significantly lower than in the control group (n=10). No differences were found in serum resistin levels between obese and control group. Fenofibrate treatment decreased serum triglyceride concentrations, while both blood glucose and glycated hemoglobin increased after three months of fenofibrate administration. Serum adiponectin or resistin concentrations were not significantly affected by fenofibrate treatment. All parameters of insulin sensitivity as measured by hyperinsulinemic-isoglycemic clamp were significantly lower in an obese diabetic group compared to the control group before treatment and were not affected by fenofibrate administration. We conclude that administration of PPAR-alpha agonist fenofibrate for three months did not significantly affect insulin sensitivity or resistin and adiponectin concentrations in obese subjects with type 2 diabetes mellitus. The lack of insulin-sensitizing effects of fenofibrate in humans relative to rodents could be due to a generally lower PPAR-alpha expression in human liver and muscle.     

The prevalence, type and severity of cardiovascular disease in diabetic and non-diabetic patients: a matched-paired retrospective analysis using coronary angiography as the diagnostic tool

People with diabetes mellitus have a 2-8-fold excess in cardiovascular mortality than people without diabetes. This study compared angiographically determined cardiovascular disease in 79 patients with diabetes mellitus and an equal number of matched controls without diabetes under the age of 55 years. Seventy-nine diabetic patients coming to coronary angiography during a 12-month period were reviewed retrospectively along with 79 control patients matched for age (+/- 3 years), sex, ethnic origin and risk factors (hyperlipidemia, body mass index and smoking history). The angiographic features of a consecutive series of 62 European and 17 Asian patients and their matched-paired controls were assessed. In all study subjects had undergone elective coronary angiography and ventriculography. Angiographic findings were graded to describe severity and extent of coronary atherosclerosis. Left ventricular systolic function was assessed by ejection fraction. The diabetic group had a significantly higher arterial systolic pressure than the non-diabetic group (p < 0.008) and they were clinically obese with a body mass index of >30. Detailed analysis of the angiograms showed that prevalence and severity of coronary artery disease in diabetic patients was greater. The mean 'severity score' was 11.66 for the diabetic group against 8.49 for the non-diabetic group (p < 0.037). Multivessel disease was more common in diabetic patients than in the controls, with three-vessel disease being the most common. Furthermore, 38 of 79 diabetic patients had three-vessel disease compared to 29 of 79 controls. Diabetic patients were also more likely to have more segments diseased in one vessel. Systolic function was reduced in the diabetic group, with a significantly lower (p < 0.05) mean ejection fraction. The present study supports the evidence that diabetic patients have more extensive coronary artery disease than non-diabetic patients and a poorer prognosis, and that the coronary arteries of the Asian patients were affected more adversely than those of the European group irrespective of the diabetic state.     

Body composition assessment in type 1 diabetes mellitus patients over 15 years old.

BACKGROUND: The aim of the present study was to assess the anthropometric characteristics and body composition in type 1 diabetic patients and compare the results with a randomly selected control population. MATERIAL AND METHODS: We studied 75 type 1 diabetic patients, 43 male and 32 female, recruited from consecutive diagnosed type 1 diabetic patients attending the Endocrine Unit and treated with a intensive insulin regimen, and 93 control subjects, 44 males and 49 females representative of the census of this city. We performed a dietary recall in patients and determined anthropometric characteristics, both in patients and controls, body weight, height, body-mass index, waist-hip ratio and body composition parameters: total body water, free-fat mass, body free-fat mass, fat mass and body fat by bioelectrical impedance analyser. RESULTS: In diabetic male patients, we observed lower waist-hip ratio than in controls, 0.84 +/- 0.06 vs. 0.88 +/- 0.07, p = 0.021, higher free-fat mass in female diabetic patients, 48.5 +/- 5.6 vs. 45.6 +/- 5.9 kg, p = 0.03, lower fat mass in male diabetic patients, 9.5 +/- 6.9 vs. 14.6 +/- 8.5 kg, p = 0.003. We did not find any correlation among the parameters of body composition and dietary macronutrient intake in patients. CONCLUSIONS: The present study exposes the differences in anthropometric characteristics and body composition in type 1 diabetes mellitus, especially lower waist-hip ratio in male, higher free-fat mass in female and lower fat mass in male.     

Visceral fat is a determinant of PAI-1 activity in diabetic and non-diabetic overweight and obese women.

Plasminogen activator inhibitor type 1 (PAI-1), an inhibitor of fibrinolysis and an important and independent cardiovascular risk factor, has been shown to be elevated in obesity and type 2 diabetes. Recent study results have suggested that adipose tissue--visceral fat in particular--could play an important role in the fibrinolytic process.In order to assess the specific role of this fat distribution, we measured PAI-1 activity (AU/ml) and visceral fat (CT-scan at level L4-L5) in 2 groups of 30 overweight and obese diabetic and overweight and obese non-diabetic women. Subjects were matched for age, weight, body mass index, fat mass and total abdominal fat. Visceral adipose tissue and PAI-1 were significantly higher in diabetic women (p = 0.022 and p = 0.004 respectively) than in non-diabetic patients. Visceral fat correlated significantly with PAI-1 activity, even after correction for insulin and triglycerides (r = 0.28, p = 0.034). Stepwise regression analysis showed visceral fat as the most important determinant factor for PAI-1 in the whole group and in the non-diabetic group. In the diabetic group, fasting insulin was the most important determinant. These results show that visceral fat is more important than BMI or total body fat in the determination of PAI-1 levels. Furthermore, the increased amount of visceral fat in type 2 diabetics may contribute to the increase of PAI-1 activity levels and the subsequent increased risk for thrombovascular disease, regardless of BMI and total fatness.     

Prospective study of incidence of juvenile diabetes mellitus over 10 years in Dar es Salaam,Tanzania.

OBJECTIVE--To ascertain the annual incidence of diabetes requiring treatment with insulin in children and adolescents aged 0-19 years in Dar es Salaam, Tanzania, during a 10 year period from 1 January 1982 to 31 December 1991. DESIGN--Prospective registration at a major urban hospital of all patients with newly diagnosed diabetes who were resident in Dar es Salaam. SETTING--Muhimbili Medical Centre, Dar es Salaam, Tanzania. PATIENTS--86 patients: 45 male, 41 female. RESULTS--The annual incidence of juvenile diabetes for both sexes was 1.5 per 100,000 population aged 0-19 years (95% confidence interval 1.3 to 1.7). Incidence per 100,000 population per year increased with age: 0.6 (0.0 to 0.13) in the age group 0-4 years, 0.5 (0.3 to 0.7) at 5-9 years, 2.2 (1.8 to 2.6) at 10-14 years, and 3.4 (2.9 to 3.9) at 15-19 years. CONCLUSION--Juvenile diabetes mellitus is fairly rare in sub-Saharan Africa. If environmental factors such as infection and material deprivation were important determinants of insulin dependent diabetes in Africans, as they may be in Europeans, much higher rates would have been expected unless genetic factors possibly exert a protective role. The eightfold greater incidence in African Americans than in Tanzanians may be related to greater genetic admixture in African Americans with people from countries in Europe with a high incidence.     

Association of obesity,diabetes, serum lipids and blood pressure regulates insulin action

Insulin resistance is present in patients with Type 2 diabetes mellitus as well as in obese patients without diabetes. The aim of our study was to compare insulin action in diabetic and control persons with or without obesity and to evaluate the influence of serum cholesterol, serum triglyceride and blood pressure on metabolic variables of insulin action. We examined 42 Type 2 diabetic patients and 41 control persons with body mass index (BMI) from 21.1 to 64.5 kg x m(-2), and 33 to 71 years old. The isoglycemic hyperinsulinemic clamp technique was performed at an insulin infusion rate of 1 mU x kg(-1) x min(-1) during 120 min. We evaluated the metabolic clearance rate of glucose (MCR(G), ml x kg(-1) x min(-1)) as the most important indicator of insulin action by isoglycemic clamp. The Pearson's correlation and multiple regression models were used to compare studied factors with the insulin action. We found following predictors of insulin resistance expressed in the relationship with MCR(G): BMI (r = -0.68, p<0.001), plasma glucose concentration (r = -0.66, p<0.001), cholesterol (r=-0.55, p<0.001), triglycerides (r = -0.54, p<0.001) and mean blood pressure (r = -0.38, p<0.01). From the multiple regression analysis we conclude that obesity may have even greater influence on the insulin action than diabetes mellitus itself.     

United Kingdom Prospective Diabetes Study (UKPDS). 13: Relative efficacy of randomly allocated diet,sulphonylurea, insulin,or metformin in patients with newly diagnosed non-insulin dependent diabetes followed for three years.

OBJECTIVE--To assess the relative efficacy of treatments for non-insulin dependent diabetes over three years from diagnosis. DESIGN--Multicentre, randomised, controlled trial allocating patients to treatment with diet alone or additional chlorpropamide, glibenclamide, insulin, or metformin (if obese) to achieve fasting plasma glucose concentrations < or = 6 mmol/l. SETTING--Outpatient diabetic clinics in 15 British hospitals. SUBJECTS--2520 subjects who, after a three month dietary run in period, had fasting plasma glucose concentrations of 6.1-14.9 mmol/l but no hyperglycaemic symptoms. MAIN OUTCOME MEASURES--Fasting plasma glucose, glycated haemoglobin, and fasting plasma insulin concentrations; body weight; compliance; and hypoglycaemia. RESULTS--Median fasting plasma glucose concentrations were significantly lower at three years in patients allocated to chlorpropamide, glibenclamide, or insulin rather than diet alone (7.0, 7.6, 7.4, and 9.0 mmol/l respectively; P < 0.001) with lower mean glycated haemoglobin values (6.8%, 6.9%, 7.0%, and 7.6%, respectively; P < 0.001). Mean body weight increased significantly with chlorpropamide, glibenclamide, and insulin but not diet (by 3.5, 4.8, 4.8, and 1.7 kg; P < 0.001). A similar pattern was seen for mean fasting plasma insulin concentration (by 0.9, 1.2, 2.4, and -0.1 mU/l; P < 0.001). In obese subjects metformin was as effective as the other drugs with no change in mean body weight and significant reduction in mean fasting plasma insulin concentration (-2.5 mU/l; P < 0.001). More hypoglycaemic episodes occurred with sulphonylurea or insulin than with diet or metformin. CONCLUSION--The drugs had similar glucose lowering efficacy, although most patients remained hyperglycaemic. Long term follow up is required to determine the risk-benefit ratio of the glycaemic improvement, side effects, changes in body weight, and plasma insulin concentration.     

Role of glycaemic control in development of microalbuminuria in patients with insulin dependent diabetes.

OBJECTIVE--To ascertain which factors determine the progression from very low rates of albumin excretion to persistent microalbuminuria in patients with insulin dependent diabetes mellitus. DESIGN--A 10 year prospective study of a cohort of diabetic patients. SETTING--Outpatient department of the Portsmouth District Hospitals. SUBJECTS--97 patients with insulin dependent diabetes mellitus who were initially free of microalbuminuria and hypertension. MAIN OUTCOME MEASURE--Urinary albumin: creatinine ratio. RESULTS--Eight of the 97 patients had developed microalbuminuria (urinary albumin:creatinine ratio > 3 mg/mmol in three consecutive early morning samples) by the 10 year follow up. The group who developed microalbuminuria had higher baseline log10 plasma glucose concentrations (mean (SD), 1.210 (0.122) v 0.984 (0.196) mmol/l, P < 0.001) and glycated haemoglobin concentrations (1.112% (0.069%) v 0.997% (0.076%), P < 0.001) and a younger age at onset of diabetes (10.0 (5.5) v 15.6 (7.8) years, P < 0.05). There was no difference in baseline duration of diabetes, smoking, sex, insulin dose, body mass index, serum creatinine concentration, or systolic, diastolic, or mean arterial blood pressure between the two groups. Multiple linear regression analysis showed that urinary albumin:creatinine ratio at 10 years was influenced by initial albumin:creatinine ratio (P = 0.006), initial glycated haemoglobin concentration (P = 0.002), and duration of diabetes (P = 0.045). Genotype for angiotensin converting enzyme was not related to the development of microalbuminuria nor, in a larger group of patients, the presence of any degree of diabetic nephropathy. CONCLUSION--In patients with insulin dependent diabetes mellitus the progression of minimal albuminuria and the development of microalbuminuria is determined primarily by poor long term glycaemic control. There is a weaker relation with longer duration of disease and younger age at onset of diabetes, but blood pressure does not seem to be implicated. Gene polymorphism for angiotensin converting enzyme is not linked to the development of microalbuminuria or established diabetic nephropathy.     

High serum fasting peptide YY (3-36) is associated with obesity-associated insulin resistance and type 2 diabetes

We studied whether serum fasting levels of active form of peptide YY (PYY), PYY(3-36), are associated with obesity and related phenotypes. The study population consisted of 428 patients with coronary artery disease and diagnosed type 2 diabetes and 440 patients with coronary artery disease but without evidence of diabetes from the ARTEMIS study. The patients were recruited from the consecutive series of patients undergoing coronary angiography in the Oulu University Hospital. The patients without diabetes underwent a 2-hour oral glucose tolerance test. PYY(3-36) levels were analyzed by human PYY(3-36) specific radioimmunoassay. Result suggested that when PYY(3-36) tertiles were considered, high serum fasting PYY(3-36) concentration was associated with high body mass index, waist circumference, hemoglobin A1c, fasting blood glucose, leptin, triglyceride (p for all p ≤ 0.001), serum insulin (p=0.013) and with a low high-density lipoprotein cholesterol (p=0.004) concentrations in the analyses adjusted for age, sex and study group. The link high PYY(3-36)-high insulin level was evident in subjects with normal glucose tolerance (p<0.05). The prevalence of diabetes was 72%, 46% and 30% in the highest, medium and lowest PYY(3-36) tertile (p<0.001). The PYY(3-36) concentrations (after adjustment for age, sex and body mass index) were higher in type 2 diabetics compared to subjects with impaired fasting glucose, impaired glucose tolerance and normal glucose tolerance (p<0.001 for trend). In conclusion, fasting PYY(3-36) concentrations in type 2 diabetic subjects are high. Although high PYY(3-36) is strongly linked to obesity and associated insulin resistance, the relation between PYY(3-36) and type 2 diabetes is independent of body fatness.     

Is diabetes mellitus related to undernutrition in rural Tanzania?

OBJECTIVE--To investigate the relation between undernutrition and diabetes. DESIGN--Survey of glucose tolerance in rural Tanzania. SETTING--Eight villages in three widely separated regions of Tanzania. SUBJECTS--8581 people aged 15 and above: 3705 men and 4876 women. MAIN OUTCOME MEASURES--Oral glucose tolerance, body mass index, height, and low haemoglobin and cholesterol concentrations. RESULTS--In the eight villages 42.7-56.9% of all men and 30.0-45.2% of all women had a body mass index below 20 kg/m2; the lowest quintile was 18.2 kg/m2 in men and 18.6 kg/m2 in women. The prevalence of diabetes did not change significantly from the lowest to the highest fifths of body mass index in men (lowest 1.6% (95% confidence interval 0.8% to 2.9%) v highest 1.3% (0.7% to 2.5%)) or women (1.1% (0.6% to 2.1%) v 0.5% (0.2% to 1.2%)). In men and in women prevalence of impaired glucose tolerance was greater in the lowest fifths of height (8.2% (6.3% to 10.6%), and 11.1% (9.2% to 13.3%)) respectively and body mass index (9.6% (7.5% to 12.1%), and 8.4% (6.7% to 10.5%)) than in the highest fifths (impaired glucose tolerance 4.7% (3.4% to 6.5%); and 5.1% (3.9% to 6.7%); body mass index 5.1% (3.7% to 7.0%), and 7.7% (6.2% to 9.6%). CONCLUSION--Rates of diabetes were not significantly associated with low body mass index or height, but overall rates were much lower than those in well nourished Western populations. Increased impaired glucose tolerance in the most malnourished people may reflect the larger glucose load per kilogram weight. The role of undernutrition in the aetiology of diabetes must be questioned.     

The Insulin Tolerance Test in Morbidly Obese Patients Undergoing Bariatric Surgery

Objective: To assess the effect of massive weight loss in relation to insulin resistance and its correlation to changes in glycemic homeostasis and lipid profile in severely obese patients. Research Methods and Procedures: A prospective clinical intervention study was carried out with 31 morbidly obese women (body mass index: 54.2 ± 8.8 kg/m²) divided into three groups according to their glucose tolerance test: 14 normal, 8 impaired glucose tolerance, and 9 type 2 diabetes. All subjects underwent an insulin tolerance test with intravenous bolus of 0.1 U insulin/kg body weight before silastic ring vertical gastroplasty Roux‐en‐Y gastric bypass surgery, and again at 2, 4, 6, and 12 months postoperatively. Fasting plasma glucose, hemoglobin A1c, and lipid profile were also evaluated. Results: A reduction of 68 ± 15% in initial excess body weight was evident within 1 year. Along with weight loss, the following statistically significant changes were found: an increase in the insulin‐sensitivity index (Kitt) and a decrease in fasting plasma glucose and hemoglobin A1c, most notably in the type 2 diabetes group. An overall improvement in lipid profile was observed in all three groups. Discussion: Bariatric surgery was an effective therapeutic approach for these obese patients because it reduced both weight and insulin resistance, along with improving metabolic parameters. Significant correlations were found between insulin resistance and metabolic improvements. Weight loss after bariatric surgery induced an improvement in metabolic fitness, related to the reduction in insulin resistance over a range of glucose tolerance statuses from normal to diabetic.     

Studies on Whole-body Potassium in Non-ketoacidotic Diabetics Before and After Treatment

Serial measurements of whole-body potassium were carried out in 28 diabetic patients, in 23 of whom diabetes had only recently been diagnosed. Eleven patients were treated with insulin, 12 with oral hypoglycaemic agents, and the rest were already on oral hypoglycaemic agents and had developed poor diabetic control; four of these required insulin. Whole-body potassium was measured before treatment was begun (or altered) and again one and six weeks later. Whole-body potassium (ratio of observed to expected) was initially reduced in most of the patients requiring insulin. After control of diabetes whole-body potassium increased significantly in the three groups. The increase in whole-body potassium in the individual patients varied over a wide range, and in patients who were treated with insulin it was often of a similar magnitude to that observed in patients in diabetic ketoacidosis.