PURPOSE: Patients with insulin-dependent diabetes mellitus (IDDM) are especially susceptible to microangiopathic complications such as nephropathy, retinopathy, and neuropathy. Microangiopathic changes are also the most important findings in histopathologic studies of the inner ear and central nervous systems in diabetic subjects. No previous studies have measured acoustic-reflex latencies (ARL) or amplitudes (ARA) in patients with IDDM. ARL and ARA reflect the function of the acoustic-reflex arch. Furthermore, possible changes in the tympanic membrane, ossicular chain, and stapedius muscle may affect the shape of acoustic-reflex. SUBJECTS AND METHODS: Acoustic-reflex thresholds, latencies, and amplitudes were studied in 53 patients with IDDM and 42 randomly selected nondiabetic control subjects, aged between 20 and 40 years, using the Madsen Model ZO 73 Impedance Bridge (Madsen Electronics, Copenhagen, Denmark). Subjects with an abnormal tympanic membrane, conductive hearing loss, and known cause for hearing impairment eg, noise damage, were excluded from the study. RESULTS: There were no differences between control and diabetic subjects in the contralateral acoustic-reflex thresholds. In contrast, patients with IDDM had longer ARLs and decreased ARAs compared with those of control subjects. ARA amplitude had linear correlation with the amplitude of tympanogram, whereas ARL had no linear correlation with auditory brainstem latencies in the same study subjects. Acoustic-reflex responses in insulin-dependent diabetic patients were not associated with the duration of diabetes, metabolic control, microangiopathy, or neuropathy. CONCLUSIONS: Prolonged ARLs and decreased ARAs in patients with insulin-dependent diabetes are probably caused more by the stiff middle ear system than disturbances in the brainstem.
Patients with NIDDM are at increased risk for coronary heart disease (CHD). However, information on the predictive value of cardiovascular risk factors and the degree of hyperglycemia with respect to the risk for CHD in diabetic patients is still limited. Therefore, we carried out a prospective study on risk factors for CHD, including a large number of NIDDM patients. At baseline, risk factor levels of CHD were determined in 1,059 NIDDM patients (581 men and 478 women), aged from 45 to 64 years. These patients were followed up to 7 years with respect to CHD events. Altogether, 158 NIDDM patients (97 men [16.7%] and 61 women [12.8%]) died of CHD and 256 NIDDM patients (156 men [26.8%] and 100 women [20.9%]) had a serious CHD event (death from CHD or nonfatal myocardial infarction). A previous history of myocardial infarction, low HDL cholesterol level ( or =5.2 mmol/l), high total triglyceride level (>2.3 mmol/l), and high fasting plasma glucose (>13.4 mmol/l) were associated with a twofold increase in the risk of CHD mortality or morbidity, independently of other cardiovascular risk factors. High calculated LDL cholesterol level (> or =4.1 mmol/l) was significantly associated with all CHD events. The simultaneous presence of high fasting glucose (>13.4 mmol/l) with low HDL cholesterol, low HDL-to-total cholesterol ratio, or high total triglycerides further increased the risk for CHD events up to threefold. Our 7-year follow-up study provides evidence that dyslipidemia and poor glycemic control predict CHD mortality and morbidity in patients with NIDDM.
The interpretation of conventional multivariate analyses concerning the relation of insulin to the risk of atherosclerotic disease is complex because of correlations of insulin with other risk factors. Therefore, we applied factor analysis to study the clustering of risk factors in the baseline data of the Helsinki Policemen Study (970 healthy men aged 34 to 64 years) and investigated whether these clusterings predict coronary heart disease (CHD) and stroke risk. Areas under the glucose and insulin response curves (AUC glucose and AUC insulin) were used to reflect glucose and insulin levels during oral glucose tolerance tests. During the 22-year follow-up, 164 men had a CHD event, and 70 men had a stroke. Factor analysis of 10 risk factor variables produced 3 underlying factors: insulin resistance factor (comprising body mass index, subscapular skinfold, AUC insulin, AUC glucose, maximal O(2) uptake, mean blood pressure, and triglycerides), lipid factor (cholesterol and triglycerides), and lifestyle factor (physical activity and smoking). In multivariate Cox models, the age-adjusted hazard ratio for insulin resistance factor during the 22-year follow-up was 1.28 (95% CI 1.10 to 1.50) with regard to CHD risk and 1.64 (95% CI 1.29 to 2.08) with regard to stroke risk. Lipid factor predicted the risk of CHD but not that of stroke, and lifestyle factor predicted a reduced CHD risk. Factor analysis including only 6 risk factor variables proposed to be central components of insulin resistance syndrome (body mass index, subscapular skinfold, AUC insulin, AUC glucose, mean blood pressure, and triglycerides) produced only a single insulin resistance factor that predicted the risk of CHD and stroke independently of other risk factors.
We investigated serum concentrations of lipoprotein subclass particles and their lipid components determined by proton nuclear magnetic resonance spectroscopy in a population-based study.
A total of 9399 Finnish men were included in the study: 3034 men with normal fasting glucose and normal glucose tolerance; 4345 with isolated impaired fasting glucose (IFG); 312 with isolated impaired glucose tolerance (IGT); 1058 with both IFG and IGT; and 650 with newly diagnosed type 2 diabetes (New DM). Lipoprotein subclasses included chylomicrons (CM) and largest VLDL particles, other VLDL particles (five subclasses), intermediate-density lipoprotein (IDL), LDL (three subclasses) and HDL (four subclasses). The phospholipid, triglyceride (TG), cholesterol, free cholesterol and cholesterol ester levels of the lipoprotein particles were measured.
Abnormal glucose tolerance (especially IGT and New DM) was significantly associated with increased concentrations of VLDL subclass particles and their components (with the exception of very small VLDL particles). After further adjustment for total TGs and HDL cholesterol, increased lipid concentrations in the CM/largest VLDL particles and in most of the other VLDL particles remained significant in individuals with isolated IGT, IFG+IGT and New DM. There was a consistent trend towards a decrease in large and an increase in small HDL particle concentrations in individuals with hyperglycaemia even after adjustment for serum total TGs and HDL cholesterol.
Abnormal glucose tolerance modifies the concentrations of lipoprotein subclass particles and their lipid components in the circulation and is also related to compositional changes in these particles.
Medial artery calcification (MAC) is a nonobstructive condition leading to reduced arterial compliance that is commonly considered as a nonsignificant finding. The aim of our study was to investigate the predictive value of MAC in relation to 7-year cardiovascular mortality, coronary heart disease (CHD) events, stroke, and lower extremity amputation in 1059 patients (581 men and 478 women) with non-insulin-dependent diabetes mellitus (NIDDM). At baseline radiologically detectable MAC in femoral arteries was found in 439 patients (41.5%) and intimal-type calcification in 310 diabetic patients (29.3%). The mean fasting plasma glucose at baseline was somewhat higher in women and the duration of diabetes somewhat longer in patients with MAC than in those without, but otherwise the presence of MAC was unrelated to conventional cardiovascular risk factors. During the follow-up 305 diabetic patients died: 208 from cardiovascular disease, 158 from CHD, and 34 from stroke. Furthermore, 58 NIDDM patients underwent their first lower extremity amputation. MAC was a strong independent predictor of total (risk factor-adjusted odds ratio and 95% confidence interval: 1.6; 1.2, 2.2), cardiovascular (1.6; 1.1, 2.2), and CHD (1.5; 1.0, 2.2) mortality, and it was also a significant predictor of future CHD events (fatal or nonfatal myocardial infarction), stroke, and amputation. This relationship was observed regardless of glycemic control and known duration of NIDDM. MAC is a strong marker of future cardiovascular events in NIDDM unrelated to cardiovascular risk factors, supporting the hypothesis that reduced arterial elasticity could lead to clinical manifestations of diabetic macroangiopathy.
Non-insulin-dependent diabetes mellitus (NIDDM) is a major risk factor for stroke in the middle-aged population, but few prospective population-based studies are available in the elderly. Moreover, the importance of metabolic control and the duration of diabetes in diabetic subjects has remained controversial. There are no previous studies on association of insulin with the risk of stroke. The present study examined whether NIDDM, its metabolic control and duration, and insulin level predict stroke.
We measured cardiovascular risk factors including glucose tolerance, plasma insulin, and glycosylated hemoglobin A1c in a Finnish cohort of 1298 subjects aged 65 to 74 years and investigated the impact of these risk factors on the incidence of both fatal and nonfatal stroke during 3.5 years of follow-up.
Of 1298 subjects participating in the baseline study, 1069 did not have diabetes and 229 had NIDDM. During the 3.5-year follow-up, 3.4% (n = 36) of nondiabetic subjects and 6.1% (n = 14) of NIDDM subjects had a nonfatal or fatal stroke. The incidence of stroke was significantly higher in diabetic women compared with nondiabetic women (odds ratio [OR], 2.25; 95% confidence interval [CI], 1.65 to 3.06). In contrast, the risk of stroke was not significantly higher in diabetic men than in nondiabetic men (OR, 1.36; 95% CI, 0.44 to 4.18). In multivariate logistic regression analyses including all study subjects, fasting and 2-hour glucose (P
The risk of stroke is known to be markedly elevated in patients with non-insulin-dependent diabetes mellitus (NIDDM), but the information on risk factors predicting stroke events in middle-aged NIDDM patients is limited. Therefore, we evaluated the significance of different cardiovascular risk factors with respect to the incidence of stroke in middle-aged NIDDM patients.
Levels of cardiovascular risk factors were determined at baseline in 1059 NIDDM patients (581 men, 478 women) and 1373 nondiabetic control subjects (638 men, 735 women), aged from 45 to 64 years, in eastern and western Finland. These patients were followed up for 7 years with respect to stroke events.
Altogether, 34 NIDDM patients (13 men, 21 women) and 5 nondiabetic subjects (4 men, 1 woman) died from stroke, and 125 NIDDM patients (61 men, 64 women) and 30 (18 men, 12 women) nondiabetic subjects had a fatal or nonfatal stroke. The risk of stroke in NIDDM men was about threefold and in NIDDM women fivefold higher than that in corresponding nondiabetic subjects. Previous history of stroke increased the risk of a new stroke event by threefold. Patients with hyperglycemia (plasma glucose > 13.4 mmol/L) and high hemoglobin A1 (> 10.7%) had about a twofold higher risk of stroke than patients with better glycemic control. Low levels of high-density lipoprotein cholesterol ( 2.30 mmol/L), and the presence of hypertension were associated with a twofold increase in the risk of stroke mortality or morbidity.
Our prospective population-based study gives evidence that previous history of stroke, hypertension, hyperglycemia, and dyslipidemia are strong predictors of stroke in middle-aged patients with NIDDM.
Prevention of Type II diabetes in subjects with impaired glucose tolerance: the Diabetes Prevention Study (DPS) in Finland. Study design and 1-year interim report on the feasibility of the lifestyle intervention programme.
AIMS/HYPOTHESIS; The aim of the Diabetes Prevention Study is to assess the efficacy of an intensive diet-exercise programme in preventing or delaying Type II (non-insulin-dependent) diabetes mellitus in subjects with impaired glucose tolerance, to evaluate the effects of the intervention programme on cardiovascular risk factors and to assess the determinants for the progression to diabetes in persons with impaired glucose tolerance.
A total of 523 overweight subjects with impaired glucose tolerance ascertained by two oral glucose tolerance tests were randomised to either a control or intervention group. The control subjects received general information at the start of the trial about the lifestyle changes necessary to prevent diabetes and about annual follow-up visits. The intervention subjects had seven sessions with a nutritionist during the first year and a visit every 3 months thereafter aimed at reducing weight, the intake of saturated fat and increasing the intake of dietary fibre. Intervention subjects were also guided individually to increase their physical activity.
During the first year, weight loss in the first 212 study subjects was 4.7 +/- 5.5 vs 0.9 +/- 4.1 kg in the intervention and control group, respectively (p