The effects of weight loss on insulin sensitivity, skeletal muscle composition and capillary density in obese non-diabetic subjects.

OBJECTIVE: To investigate whether the improvement in insulin resistance by weight loss is associated with changes in skeletal muscle fiber composition or capillary density. DESIGN: Longitudinal, clinical intervention study of a 2.1 MJ diet daily for 3 weeks and 3.4 MJ diet daily for 9 weeks. SUBJECTS: Seven obese (age: 41-59 y, five men, BMI > 34 kg/m2) non-diabetic subjects. MEASUREMENTS: Insulin action was measured by the euglycaemic hyperinsulinaemic clamp before and after 3 and 12 weeks of the very low calorie diet. In addition, the skeletal muscle biopsies were taken before and after the 12 weeks. RESULTS: During the 12 weeks, the subjects lost about 16% of body weight. The weight loss was accompanied by a nearly two-fold increase in total body glucose disposal rate (GDR; baseline vs 12 weeks: 842 +/- 91 vs 1505 +/- 242 mu mol/m2/min; p < 0.05). Most marked improvement was observed in non-oxidative component of GDR, which increased 2.7-fold as compared to baseline (292 +/- 113 vs 788 +/- 231 mu mol/m2/min; p < 0.05). However, no significant change in proportion of type II fibers as well as in skeletal muscle capillary density occurred during the study. CONCLUSION: In obese non-diabetic subjects the improvement in insulin sensitivity induced by weight loss was not accompanied by marked changes in skeletal muscle fiber composition or capillary density. However, due to small number of subjects studied, the role of structural changes in the muscle fiber composition cannot be entirely ruled out.

Natural history of peripheral neuropathy in patients with non-insulin-dependent diabetes mellitus.

BACKGROUND: There is little information on the incidence and natural history of neuropathy in patients with non-insulin-dependent diabetes mellitus (NIDDM). METHODS: We studied patients with newly diagnosed NIDDM and control subjects both at base line and 5 and 10 years later. Polyneuropathy was diagnosed on the basis of clinical criteria (pain and paresthesias) and electrodiagnostic studies (nerve conduction velocity and response-amplitude values). We investigated the relation between metabolic variables (results of oral glucose-tolerance tests, serum lipid and insulin concentrations, and glycosylated hemoglobin values) and the development of polyneuropathy. RESULTS: In 10 years, 36 patients with NIDDM and 8 control subjects died; 86 patients and 121 control subjects completed the study. When the study ended, 18 percent of the patients were being treated only with diet, 59 percent with oral hypoglycemic drugs alone, 12 percent with insulin alone, and 11 percent with both insulin and oral hypoglycemic agents. At base line the prevalence of definite or probable polyneuropathy among the patients with NIDDM was 8.3 percent, as compared with 2.1 percent among the control subjects. These values 10 years later were 41.9 percent and 5.8 percent, respectively. The number of patients with NIDDM who had nerve-conduction abnormalities in the legs and feet increased from 8.3 percent at base line to 16.7 percent after 5 years and to 41.9 percent after 10 years. The decrease in sensory and motor amplitudes, indicating axonal destruction, was more pronounced than the slowing of the nerve conduction velocities, which indicates demyelination. Among the patients with NIDDM, those with polyneuropathy had poorer glycemic control than those without. Low serum insulin concentrations before and after the oral administration of glucose were associated with the development of polyneuropathy, regardless of the degree of glycemia. CONCLUSIONS: The prevalence of polyneuropathy among patients with NIDDM increases with time, and the increase may be greater in patients with hypoinsulinemia.

Medial artery calcification predicts cardiovascular mortality in patients with NIDDM.

OBJECTIVE: To study the predictive value of medial artery calcification (Mönckeberg's sclerosis) in relation to 10-year cardiovascular mortality in patients with non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: We studied the predictive value of thigh medial and intimal artery calcifications to 10-year cardiovascular mortality in a well-characterized group of 133 middle-aged, newly diagnosed patients with NIDDM (70 men and 63 women). RESULTS: At baseline, medial artery calcifications were found in 17% of the patients and intimal-type calcifications were found in 23%. During the follow-up, 21% of the diabetic patients died from cardiovascular causes. The age-adjusted odds ratio for cardiovascular mortality was 4.2 (95% confidence intervals: 1.5-11.3) for medial-type and 1.6 (0.6-4.3) for intimal-type calcifications. In multiple logistic regression analysis, including age, sex, systolic blood pressure, low-density- and high-density-lipoprotein cholesterol, very-low-density lipoprotein triglycerides, smoking, body mass index, fasting serum insulin, blood glucose, urinary albumin, and ischemic ECG changes, as well as the intimal artery calcification, the medial artery calcification was the dominant factor predicting cardiovascular mortality. CONCLUSIONS: In this study medial artery calcification was a strong independent predictor of cardiovascular mortality in patients with newly diagnosed NIDDM. Whether these subjects had a longer duration of hyperglycemia before the diagnosis than those without medial artery calcifications remains unknown.

Metabolic evolution of type 2 diabetes: a 10-year follow-up from the time of diagnosis.

OBJECTIVES: To investigate fasting and post-load plasma glucose, insulin and C-peptide levels during oral glucose tolerance tests in patients with type 2 diabetes and in control subjects, and the metabolic evolution of the diabetes. DESIGN, SETTING AND SUBJECTS: A 10-year prospective study consisting of a representative group of 133 (70 men, 63 women) newly diagnosed type 2 diabetic patients diagnosed at health centres between 1979 and 1981 and 144 (62 men, 82 women) nondiabetic control subjects recruited from the population register. At baseline, diabetic subjects were treated with diet only. The subjects were studied at baseline and after 5 and 10 years. MAIN OUTCOME MEASURES: The changes in plasma glucose, insulin and C-peptide levels in diabetic and control subjects at baseline and after 5 and 10 years follow-up. Factors associated with the decline in insulin and C-peptide levels in diabetic patients (e.g. metabolic control, islet cell antibodies). RESULTS: A slight increase in glucose levels was seen during the follow-up in both diabetic with diet and/or oral drug treated patients, but post-glucose insulin (and C-peptide and 5- and 10-year examination) levels declined in diabetic patients; this was opposite to the controls, in whom the levels tended to increase. The decline in insulin levels (area under the curve) during the follow-up was greatest in those diabetic patients with poor metabolic control during the follow-up. The cumulative incidence of requirement for insulin based on various cut-off levels for post-glucagon C-peptide nearly doubled between the 5- and 10-year examinations. Islet cell antibodies were predictive of insulin deficiency. CONCLUSIONS: Type 2 diabetes was characterized by progressive impairment of insulin response to glucose and this decline was associated with poor metabolic control of diabetes.

Metabolic and dietary determinants of serum lipids in obese patients with recently diagnosed non-insulin-dependent diabetes.

The aim of the study was to ascertain the metabolic and dietary determinants of changes in serum lipids during a 15-month diet therapy of obese patients (n = 71, 41 males, 30 females) with recently diagnosed Type 2 (non-insulin-dependent) diabetes. The subjects lost weight and improvement in glycaemic control was observed, but due to variation in individual responses the mean serum total cholesterol or non-HDL cholesterol did not change significantly. The proportion of palmitic acid decreased and that of linoleic acid increased in serum lipids during the study, and serum triglycerides decreased and HDL-cholesterol increased. In univariate analyses, decreased serum triglyceride level was associated with serum triglycerides at baseline, decreases in body mass index, fasting blood glucose and palmitic acid proportion of serum triglycerides, and the intake of saturated fats and dietary fibre, but in multiple regression analyses the determinants for decreased serum triglycerides were high serum triglycerides at baseline and a decreased proportion of palmitic acid in serum triglycerides. In univariate analysis, increased HDL-cholesterol was associated with the baseline HDL-cholesterol, decrease in the triceps/subscapularis ratio and the intake of saturated and mono-unsaturated fatty acids, but none of these variables had an independent contribution to the increase in serum HDL-cholesterol in multiple regression analysis. In conclusion, a reduction of palmitic acid in the serum lipids, which was probably due to reduction of dietary saturated fatty acids, had beneficial effects on serum lipids in obese patients with Type 2 diabetes, independently of weight loss and improvement in glycaemic control.

Ten-year cardiovascular mortality in relation to risk factors and abnormalities in lipoprotein composition in type 2 (non-insulin-dependent) diabetic and non-diabetic subjects.

The purpose of the present study was to examine 10-year cardiovascular morbidity and mortality in patients with newly-diagnosed Type 2 (non-insulin-dependent) diabetes mellitus and non-diabetic control subjects and to evaluate the effects of general risk factors, plasma insulin, urinary albumin excretion, lipoprotein abnormalities characteristic of Type 2 diabetes and the degree of hyperglycaemia in diabetic patients on cardiovascular mortality. Furthermore, the extent to which the above-mentioned factors could contribute to the excessive cardiovascular mortality observed in diabetic patients was examined. In the years 1979-1981, altogether 133 (70 men, 63 women) newly-diagnosed patients with Type 2 diabetes and 144 (62 men, 82 women) non-diabetic control subjects aged 45-64 years were studied. Both groups were re-examined in the years 1985-1986 and 1991-1992. The impact of different factors on cardiovascular mortality was examined by univariate analyses after adjustment for age and sex and by multiple logistic regression analyses. The age-standardized total and cardiovascular mortality rates were substantially higher in diabetic men (17.8 and 15.0%, total and cardiovascular mortality, respectively p = 0.06 and NS) and women (18.5 and 16.6%, p < 0.01 for both) than in non-diabetic control men (5.2% both total and cardiovascular mortality) and women (4.2 and 2.2%). Cardiovascular mortality was not related to the treatment modality (diet, oral drugs, insulin) at 5 years from diagnosis. Use of diuretics, beta-blocking agents or their combination at baseline did not make a significant contribution to cardiovascular mortality either. In multiple logistic regression analysis on diabetic patients, age, LDL triglycerides, smoking, blood glucose and ischaemic ECG at baseline had independent associations with cardiovascular mortality. Interestingly, urinary albumin excretion rate measured at 5-year examination also predicted 10-year cardiovascular mortality after adjustment for the effects of major risk factors including lipoprotein abnormalities, but its predictive power reduced to a nonsignificant level when the effect of plasma glucose was taken into account. The relative risk of cardiovascular mortality associated with diabetes was 8.2 after allowing for age alone, but it declined to 3.7 when all contributing factors from the baseline examination (except blood glucose) were taken into account. In conclusion, the present results indicate that LDL triglycerides and/or other changes in lipoprotein composition characteristic of Type 2 diabetes and manifesting as elevated serum triglycerides are atherogenic and they strongly predict increased cardiovascular mortality.(ABSTRACT TRUNCATED AT 400 WORDS)

The maintenance of improved metabolic control after intensified diet therapy in recent type 2 diabetes.

Altogether 86 patients with recently diagnosed NIDDM, aged 40-64 years were randomised after 3 months of basic education to intensified diet (Int. group, 21 men, 19 women) or conventional treatment groups (Conv. group, 28 men, 18 women). The aim was to examine whether an intensified diet education would result in a better metabolic control and greater reduction in cardiovascular risk factors than conventional treatment for obese patients with recently diagnosed type 2 diabetes mellitus. Furthermore, both groups were re-examined after a second year of observation period to find out the maintenance of the results after intervention. After basic education, Int. group participated in 12-months diet education, while Conv. group was treated in local health centres. During the intervention period, only Int. group showed further weight reduction. Only 20% of patients in Int. and 6% of patients in Conv. group had BMI < 27 kg/m2 at the end of the intervention, while 75% of patients in Int. and 52% of patients in Conv. group had achieved a good metabolic control (fasting blood glucose < 6.7 mmol/l; P = 0.005 between groups). Serum total cholesterol did not change significantly, but the changes in HDL-cholesterol, triglycerides and apolipoprotein B level were significant in Int. group only. The proposed acceptable values for serum lipids were achieved by 52 to 88% of patients without major differences between the two groups. During the second year of observation, weight gained in both groups and a deterioration was seen in metabolic control. Despite that a greater proportion of patients in the Int. group still was in good metabolic control (55.3% vs. 31.8%, P = 0.016), furthermore Int. group was receiving less frequently oral drugs for hyperglycaemia than Conv. group. No differences in serum lipids were observed between the groups after the observation period. HDL-cholesterol showed a persistent improvement in both groups.

Nerve function and its determinants in patients with newly-diagnosed type 2 (non-insulin-dependent) diabetes mellitus and in control subjects--a 5-year follow-up.

In order to assess the changes in nerve function 5 years after the diagnosis of diabetes mellitus and the determinants of progression of neuropathy, we studied 113 Type 2 (non-insulin-dependent) diabetic patients and 127 non-diabetic control subjects. Motor and sensory nerve conduction velocities were measured at the time of diagnosis of diabetes and 5 years later. At both examinations conduction velocities and response amplitudes were lower in diabetic patients than in control subjects. During the follow-up sural nerve conduction was impaired in both diabetic and control subjects, but, in general, changes in neurophysiological parameters were slight and inconsistent. In 12 diabetic patients nerve function deteriorated significantly during the follow-up. These patients had higher glycaemic indices at both examinations and lower baseline blood pressure levels as compared to the rest of the diabetic patients. No differences between these patient groups were found in other baseline risk factors (age, obesity, use of alcohol, smoking, serum insulin levels, albuminuria, lipids). In conclusion, Type 2 diabetic patients have disturbed nerve function at the time of diagnosis, but neurophysiological impairment during the next 5 years is on the average slight. Poor glycaemic control seems to be the most important risk factor in the deterioration of nerve function in these patients.

Effect of metabolic control on autonomic function in obese patients with newly diagnosed type 2 diabetes.

To evaluate the effect of diet therapy and physical exercise on autonomic nervous function in newly diagnosed Type 2 diabetes, we followed 83 middle-aged obese patients (48 men, 35 women) for a 15-month period. After a 3-month basic education programme the patients were randomized to one of two groups for comparison of standard treatment given by community health centres (conventionally treated group) and intensive dietary and exercise education (intervention group). Autonomic function was assessed by heart rate variability during deep breathing (expiration/inspiration ratio, E/I), and by systolic blood pressure response to standing up. The intensively treated women (n = 18) had the best blood glucose throughout the study, and this was the only group to show an improvement in E/I ratio (1.19 +/- 0.03 vs 1.30 +/- 0.05, mean +/- SEM, p < 0.05). None of the groups showed any significant change in systolic blood pressure response to standing up. For further analyses, the original groups were combined and thereafter divided into those with declining fasting blood glucose during the intervention phase (n = 39) and into those with no change or increase in blood glucose level (n = 44). The group with improving blood glucose level showed an increase in E/I ratio (1.22 +/- 0.02 vs 1.28 +/- 0.03, p < 0.01) while in the other group E/I ratio remained unchanged (1.21 +/- 0.02 vs 1.20 +/- 0.02). The difference in E/I ratio between these two groups was significant at 15 months (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Lower-extremity amputations in diabetic and nondiabetic patients. A population-based study in eastern Finland.

OBJECTIVE: To study the incidence of LEAs attributable to PVD in diabetic and nondiabetic patients. The age at first amputation, the level of amputation, the number of reamputations, and survival after amputation also were examined in the study populations. RESEARCH DESIGN AND METHODS: This retrospective study was based on a population of 253,000 inhabitants in eastern Finland. All patients with their first LEA performed during the period from 1 January 1978 to 31 December 1984 were identified from the registers of operation theaters in the study area. Furthermore, patient records and death certificates were reviewed. Amputations attributable to causes other than evident atherosclerotic vascular disease were excluded. RESULTS: Altogether, 477 patients (85 diabetic men, 127 nondiabetic men, 169 diabetic women, and 96 nondiabetic women) were identified. The overall LEA rate was 26.9/100,000 per yr, and the incidence increased strongly with age in both diabetic and nondiabetic patients. The age-adjusted amputation incidence per yr was 349.1/100,000 for diabetic men, 33.9/100,000 for nondiabetic men, 239.4/100,000 for diabetic women, and 17.2/100,000 for nondiabetic women. The proportion of peripheral (toe, leg) amputations was markedly higher in diabetic patients who also tended to have more reamputations during the follow-up than did nondiabetic subjects. The diabetic status per se was a statistically significant risk factor for mortality in women, but not in men. CONCLUSIONS: Diabetic men and women had a 10.3- and 13.8-fold higher risk, respectively, for LEA.

Relationship between hyperglycaemia and aerobic power in men with newly diagnosed type 2 (non insulin-dependent) diabetes.

The aim of the study described here was to evaluate aerobic function during exercise and its determinants in middle-aged men with newly diagnosed Type 2 (non insulin-dependent) diabetes. Using breath-by-breath technique, we measured O2 uptake at anaerobic (ventilatory) threshold and at peak exercise in a group of diabetic men (n = 19; fasting blood glucose 8.6 +/- 0.7 mmol l-1, mean +/- SEM) without any disease or medication that could have had an influence on exercise performance, and compared the results to those observed in non-diabetic healthy control men (n = 18). There were no differences in physical activity or smoking habits between the groups. Oxygen uptake was lower in the diabetic men than in the control men both at anaerobic threshold (15.0 +/- 0.8 vs. 18.8 +/- 1.0 ml min-1 kg-1, P < 0.01) and at peak exercise (25.3 +/- 1.5 vs. 31.1 +/- 1.4 ml min-1 kg-1, P < 0.01). In the diabetic men peak O2 uptake showed an inverse linear correlation with age (r = -0.71, P < or = 0.001), fasting blood glucose (r = -0.49, P < 0.05) and glucose response in an oral glucose tolerance test (r = -0.43, P < 0.05). In addition, long-term smoking was associated with impaired peak O2 uptake. In a stepwise multiple regression procedure 75% of the total variance of peak O2 uptake in the diabetic men was explained by age, post-load blood glucose response and smoking history. Thus, in addition to ageing and smoking, hyperglycaemia is correlated with impaired aerobic power in men with newly diagnosed Type 2 diabetes.

Chromium supplementation in impaired glucose tolerance of elderly: effects on blood glucose, plasma insulin, C-peptide and lipid levels.

Altogether twenty-six elderly subjects (aged 65-74 years) with persistent impaired glucose tolerance (World Health Organization (1985) criteria) identified in a population-based study, were randomly treated either with chromium-rich yeast (160 micrograms Cr/d) or with placebo for 6 months. The 24 h urinary Cr increased from 0.13 (SE 0.03) to 0.40 (SE 0.06) micrograms/d in the Cr group (n 13) but no change was found in the placebo group (n 11) (0.13 (SE 0.02) v. 0.11 (SE 0.02) micrograms/d). No significant change was observed in the oral glucose tolerance test (glucose dose 75 g; 0, 1 and 2 h blood glucose respectively): 5.3 (SE 0.1), 9.3 (SE 0.3), 8.2 (SE 0.3) mmol/l v. 5.0 (SE 0.1), 8.5 (SE 0.4), 7.3(SE 0.5) mmol/l in the Cr group; 4.9 (SE 0.2), 9.2 (SE 0.6), 8.1 (SE 0.3) mmol/l v. 4.8 (SE 0.2), 8.5 (SE 0.5), 7.0 (SE 0.6) mmol/l in the placebo group (baseline v. 6 months). Glycosylated haemoglobin, plasma insulin, C-peptide and apolipoprotein A1 and B levels remained unchanged, and no improvement was seen in serum total cholesterol (6.2 (SE 0.3) v. 6.4 (SE 0.3) mmol/l for the Cr group, 6.2 (SE 0.4) v. 6.5 (SE 0.3) mmol/l for the placebo group), high-density-lipoprotein-cholesterol (1.1 (SE 0.1) v. 1.2 (SE 0.1) mmol/l for the Cr group, 1.0 (SE 0.1) v. 1.1 (SE 0.1) mmol/l for the placebo group) or triacylglycerols (2.5 (SE 0.4) v. 2.0 (SE 0.4) mmol/l for the Cr group, 2.4 (SE 0.2) v. 2.5 (SE 0.2) mmol/l for the placebo group). The present results indicate that Cr supplementation does not improve glucose tolerance or serum lipid levels in elderly subjects with stable impaired glucose tolerance.

Habitual physical activity, aerobic capacity and metabolic control in patients with newly-diagnosed type 2 (non-insulin-dependent) diabetes mellitus: effect of 1-year diet and exercise intervention.

The aim of this study was to assess the effects of a 1-year intensified diet and exercise education regimen on habitual physical activity and aerobic capacity in middle-aged, obese patients with newly-diagnosed Type 2 (non-insulin-dependent) diabetes mellitus. In addition, we analysed whether the level and the changes in physical activity and aerobic capacity are related to the metabolic control of diabetes. After a 3-month basic education programme, 78 patients (45 men, 33 women) were randomly placed in an intervention or conventionally treated group. The intervention group received intensified diet education and continuous encouragement to increase physical activity which was monitored using exercise records and questionnaires. Aerobic capacity was assessed by measuring oxygen uptake at anaerobic threshold and at peak exercise. The proportion of patients with regular recreational exercise increased from 24% to 38% in the intervention men (0.10 less than p less than 0.20), remained at 54% in the conventionally treated men, increased from 53% to 70% in the intervention women (0.10 less than p less than 0.20) and from 31% to 50% (0.10 less than p less than 0.20) in the conventionally treated women. No measurable improvement was found in oxygen uptake in any of the groups. When the groups were combined, HbA1c showed an inverse correlation with oxygen uptake at anaerobic threshold (r = 0.27, p less than 0.01) and maximum oxygen uptake (r = 0.28, p less than 0.01) at 12 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Hyperglycaemic symptoms before diagnosis of non-insulin-dependent (type 2) diabetes mellitus in relation to 5-year outcome.

A group of newly diagnosed patients with non-insulin-dependent (type 2) diabetes mellitus (n = 133) were divided into two groups according to the symptoms of diabetes mellitus at diagnosis; a group (26 men and 17 women) with hyperglycaemic symptoms (polydipsia, polyuria, weight loss and tiredness) and a group (44 men and 46 women) without such symptoms. At the time of diagnosis, symptomatic patients tended to be leaner (P = NS), and they were more hyperglycaemic (P less than 0.001-0.06) and had lower insulin responses to an oral glucose load (P less than 0.01-0.05) than asymptomatic patients, but after 5 years no difference in these respects was found. No significant differences in the frequency of islet-cell antibodies or cardiovascular diseases were found between the two diabetic groups. At the 5-year examination, the initially symptomatic patients were receiving pharmacological treatment for hyperglycaemia more often than asymptomatic patients. No consistent differences in clinical characteristics and 5-year outcome were observed between those diabetic patients who were diagnosed on the basis of hyperglycaemic symptoms and those who were diagnosed for other reasons. In conclusion, in middle-aged patients with newly diagnosed diabetes mellitus classified as non-insulin-dependent, diabetic symptoms at diagnosis did not predict the 5-year outcome of the patients in terms of metabolic control or cardiovascular events.

Epidemiological considerations in the prevention of coronary heart disease among the elderly.

Coronary heart disease is a major health problem among the elderly, the importance of which increases with the rising proportion of old people. The significance of traditional cardiovascular risk factors has been documented in younger age groups, and it seems they are effective at least in 'young' elderly people (aged between 65 and 80 years), whereas their role is less well known in people over 80 years because other end-points such as stroke and cancer become increasingly important and coronary heart disease cannot be considered in isolation. Pharmacological treatment of hypertensive elderly patients can reduce the incidence of strokes significantly, but reduction of coronary heart disease incidence is less clear. There are many uncertainties relating to lipid-lowering medication in old people. Nonpharmacological means (modest lifestyle, healthy diet and regular exercise) are unlikely to be of harm in the prevention of coronary heart disease in the elderly.

Five-year follow-up of islet cell antibodies in type 2 (non-insulin-dependent) diabetes mellitus.

The aim was to study the frequency and appearance of cytoplasmic islet cell antibodies in relation to impairment of insulin secretory capacity and some clinical characteristics in a representative group of middle-aged (45-64 years) patients with Type 2 (non-insulin-dependent) diabetes mellitus (70 male, 63 female) at the time of diagnosis and at five-year follow-up. Non-diabetic control subjects (62 male, 82 female) were similarly examined at five-year intervals. At the baseline five out of 133 (3.8%) diabetic patients were positive for conventional and four (3.0%) for complement-fixing islet cell antibodies. Ten patients had become positive by the second screening for conventional antibodies and six for complement-fixing antibodies, but none showed negative conversion. Two non-diabetic subjects (1.5%) became antibody positive during the follow-up. Insulin treatment was started during the follow-up for four out of 15 (27%) conventional antibody positive and for one out of 121 (0.8%) antibody negative diabetic patients (p = 0.001). The sensitivity of the positive conventional and complement-fixing antibody for identifying patients who developed an impairment of insulin secretory capacity (post-glucagon C-peptide less than or equal to 0.60 nmol/l at 5-year) was 75%. The respective specificity was 90% and the positive predictive values were highest in the case of high positivity (50%). The negative predictive value of antibody positivity was close to 100%. In conclusion, islet cell antibody positivity in patients classified as Type 2 was persistent during the follow-up and predicted the future development of insulin deficiency especially in those patients with high or increasing antibody titres.

Effect of diet therapy on maximum aerobic power in obese, hyperglycaemic men with recently diagnosed type 2 diabetes.

To find out the effect of correction of hyperglycaemia on maximum aerobic power and anaerobic threshold, we studied 40 middle-aged obese men with recently diagnosed type 2 diabetes before and after 3 months diet therapy. Respiratory gas exchange was measured during maximal incremental bicycle exercise test with breath-by-breath technique at rest, at anaerobic threshold and at peak exercise. As a whole group, the diabetic men reached higher work load after therapy (+9 +/- 3 W (mean +/- SEM), p less than 0.01). A weak inverse linear correlation was found between the changes in fasting blood glucose and in maximum oxygen uptake (r = -0.29, p less than 0.05). When the patients were divided into two groups according to the median values in the change in fasting blood glucose, only those men with more than 1 mmol l-1 decrease in fasting blood glucose improved maximum oxygen uptake (+124 +/- 55 ml min-1 or +6%, p less than 0.05). Oxygen uptake at anaerobic threshold did not change significantly. These results suggest that the correction of hyperglycaemia by diet therapy may improve maximal aerobic power in obese men with recently diagnosed type 2 diabetes.

Aortic and lower limb artery calcification in type 2 (non-insulin-dependent) diabetic patients and non-diabetic control subjects. A five year follow-up study.

The purpose of the present study was to assess among a representative group of middle-aged newly diagnosed type 2 diabetics and control subjects the baseline prevalence and 5-year incidence of arterial calcifications of aorta and lower limb and their relationship to cardiovascular morbidity. The relationship of baseline risk factors to the development of arterial calcifications was also studied. At the time of diagnosis the age-adjusted prevalence of aortic and lower limb intimal calcifications was higher in diabetics than in control subjects (aortic calcifications: 29 vs. 17% for men, P = 0.05; 26 vs. 19% for women, P = 0.06; lower limb intimal calcifications: 24 vs. 12% for men, P = 0.02; 10 vs. 7% for women; P = NS), whereas no significant difference in baseline prevalence of lower limb medial calcifications was observed (15 vs. 21% for men, 9 vs. 10% for women). The 5-yr incidence of aortic calcifications in both sexes and of lower limb calcifications in men was similar in diabetic and control subjects, but the incidence of lower limb calcifications was higher in diabetic women than in control women (intimal: 33 vs. 11%, P = 0.009: medial: 29 vs. 14%, P = 0.05). The baseline prevalence of abdominal aortic (37 vs. 22%, P = NS for diabetics; 42 vs. 16%, P = 0.02 for control subjects), lower limb intimal (24 vs. 16% for diabetics, P = NS; 15 vs. 7% for control subjects, P = NS) and medial calcifications (23 vs. 7% for diabetics, P = 0.03) were higher in subjects who developed intermittent claudication during the follow-up than in those free of it at the 5-yr examination. Abnormalities in VLDL-metabolism and high systolic blood pressure were associated with the development of aortic calcification in diabetic subjects. In conclusion, already at the time of diagnosis atherosclerotic calcifications are more prevalent in type 2 diabetics than in nondiabetic subjects. During the follow-up diabetic women, but not men, had higher incidence of lower limb intimal and medial calcifications than non-diabetic subjects. Arterial calcifications tended to be associated with the development of intermittent claudication during the follow-up in diabetic and control subjects.

5-year incidence of atherosclerotic vascular disease in relation to general risk factors, insulin level, and abnormalities in lipoprotein composition in non-insulin-dependent diabetic and nondiabetic subjects.

The 5-year incidence of myocardial infarction and claudication was examined in a group of middle-aged patients (n = 133, 70 men and 63 women) with newly diagnosed non-insulin-dependent diabetes and nondiabetic control subjects (n = 144, 62 men and 82 women). The effects of general risk factors, plasma insulin level, and lipoprotein abnormalities on the incidence of myocardial infarction and claudication were also evaluated by univariate analyses in both diabetic patients and nondiabetic subjects and by multivariate analyses combining both groups. The age-adjusted incidence of myocardial infarction was higher both in diabetic men (19.4%) and diabetic women (11.0%) than in nondiabetic men (3.2%, p = 0.009) and nondiabetic women (3.0%, p = 0.047). Similarly, the age-adjusted incidence of claudication was higher among the diabetic patients (20.3% vs. 8.0% for men, p = 0.06; 21.8% vs. 4.2% for women, p = 0.003). None of the general risk factors (i.e., low density lipoprotein [LDL] cholesterol, blood pressure, smoking, and high density lipoprotein [HDL] cholesterol) showed an association with the risk of myocardial infarction either in the diabetic or nondiabetic groups of subjects, but an ischemic electrocardiographic abnormality at the baseline examination predicted myocardial infarction in diabetic men. In univariate analyses in diabetic subjects, high serum total cholesterol, low HDL cholesterol, high very low density lipoprotein (VLDL) cholesterol, and high total, LDL and VLDL triglycerides, and in nondiabetic subjects, high VLDL cholesterol and LDL triglycerides were associated with the appearance of claudication. In multivariate analyses including both diabetic and control subjects, only diabetes had an independent association with myocardial infarction, whereas smoking, high LDL triglycerides or VLDL cholesterol, and high fasting plasma insulin showed independent relations to claudication. The present results indicate that changes in lipoprotein composition characteristic of non-insulin-dependent diabetes are atherogenic and increase the risk of atherosclerotic vascular disease. Furthermore, high plasma insulin might also be involved in atherogenesis, independent of lipoprotein abnormalities.