G. Blohmé

Adipose Tissue Fat Cell Size and Number in Relation to Metabolism in Randomly Selected Middle-Aged Men and Women

Abstract Body fat, adipose tissue fat cell size and number, plasma lipids, and glucose tolerance with plasma insulin were determined in randomly selected middle-aged men and women and in young men. Body fat correlated with both fat cell size and number. The associations with fat cell size were apparently somewhat stronger than with fat cell number. Middle-aged women had higher body fat than middle-aged men, but no difference could be demonstrated in fat cell size or number. Subjects whose weight was stable were characterized by a normal number of small fat cells. In middle-aged men, fat cell size correlated with plasma insulin concentration. The latter in combination with decreased glucose tolerance was associated with increased plasma triglyceride concentration. In women, none of these associations were found.

Fasting Serum Insulin Concentration and Early Insulin Response as Risk Determinants for Developing Diabetes

Among a cohort of 348 women aged 50 on entering a 12‐year prospective study, the incidence of diabetes was increased (17.1%) during follow‐up in those who initially had fasting glucose concentration above the upper quintile, a fasting serum insulin concentration above the upper quintile (14.9%), a disappearance rate of glucose below the lowest quintile in an IV glucose tolerance test (12.7%), or early insulin response below the lowest quintile (17.1%). The incidence in all women was 4.9%. By multivariate analysis, the highest risk was for high fasting serum insulin concentration. Obesity and treatment with antihypertensive drugs further increased the risk. An initial low early insulin response was not however a prerequisite for the development of manifest diabetes. Determination of fasting insulin concentration, especially in overweight hypertensive subjects, is of value in order to find out which subjects are at high risk of developing diabetes.

Impact of metabolic control in progression of clinical diabetic nephropathy

SummaryRenal clearance of 51Cr-EDTA as a measure of glomerular filtration rate was followed prospectively for 21 months in 18 Type 1 (insulin-dependent) patients with juvenile-onset diabetes and nephropathy. Hypertension was treated aggressively, attaining a mean blood pressure of 154/88 mmHg in the supine and 126/82 mmHg in the standing position. The mean glycosylated haemoglobin value (HbA1c) during the observation period was found to correlate well with the mean of random blood glucose values (r=0.72). It also correlated to the rate of glomerular filtration rate decline over time, whether the latter was calculated as slope coefficient for all available data (r=-0.52, p<0.05) or based on the first and last observations only (r=-0.57, p<0.05). In a multiple linear stepwise regression analysis also including mean arterial blood pressure, the correlation between glomerular filtration rate decline and HbA1c was significant at p<0.01; this explained one-third of the progression, while mean arterial pressure could not be shown to contribute. It is concluded that hyperglycaemia, contrary to the general belief, is a risk factor for the progression of clinical diabetic nephropathy with reduced glomerular filtration rate.

Male predominance of type 1 (insulin-dependent) diabetes mellitus in young adults : results from a 5-year prospective nationwide study of the 15-34 year age group in Sweden

SummaryThe incidence of diabetes mellitus in Sweden in the 15–34 year age group was prospectively studied on a nationwide basis, beginning 1 January 1983. A total of 1,214 male and 720 female cases of newly-diagnosed (excluding gestational) diabetes were reported over a 5-year period. This corresponds to an incidence of 20.5 per 100,000/year in male subjects and 12.7 per 100,000/year in female subjects. Most cases were classified as Type 1 (insulin-dependent) diabetes, with an incidence of 15.9 in males and 8.6 in females. The incidence of Type 1 diabetes decreased gradually with age, while the incidence of Type 2 (non-insulin-dependent) diabetes increased. A male predominance was found in all age groups, with a male-to-female ratio of 1.8∶1 for Type 1 diabetes and 1.3∶1 for Type 2 diabetes. Maximum blood glucose concentration at diagnosis was significantly higher in males than in females in both Type 1 and Type 2 diabetic subjects. In contrast, the percent desirable weight was significantly higher in females, both in Type 1 and Type 2 diabetic subjects. The difference in diabetes incidence therefore cannot be attributed to any methodological error. The present finding of a marked male predominance after puberty in Type 1 diabetes in an ethnically quite homogeneous population supports the hypothesis that environmental risk factors and life-style are important for the development of the disease.

Gender differences and temporal variation in the incidence of type 1 diabetes: results of 8012 cases in the nationwide Diabetes Incidence Study in Sweden 1983-2002.

Objectives.  To establish the gender difference amongst newly diagnosed type 1 diabetic patients aged 15–34 years, considering age at diagnosis, temporal trend and seasonal variation at time of diagnosis.

Altered Recognition of Hypoglycaemic Symptoms in Type I Diabetes during Intensified Control with Continuous Subcutaneous Insulin Infusion

The effect of intensified metabolic control obtained with continuous subcutaneous insulin infusion (CSII) on the frequency and symptoms of hypoglycaemia was studied in type I diabetic patients. The reproducibility of the questionnaire used to evaluate the hypoglycaemic symptoms was verified in a control group receiving unchanged conventional insulin therapy for 2 months. Metabolic control was significantly improved during CSII (HbA1c 6.8 ± 0.4% versus 8.7 ± 0.7%, normal range up to 5.4%) in all patients while no change was seen in the control group. The results of frequent self glucose monitoring showed that the incidence of low glucose levels (below 3.5 mmol/l) increased about threefold in the CSII group. Awareness of hypoglycaemia was clearly changed during CSII with less pronounced adrenergic symptoms while no alterations were found in the group with unchanged metabolic control. These results emphasize the importance of regular self glucose monitoring during CSII and of informing the patients that their hypoglycaemic symptoms may change during intensified control.

Difficulties in Classifying Diabetes at Presentation in the Young Adult

All newly diagnosed diabetic patients in Sweden aged 15–34 years have been registered since 1983. In this study the clinical characteristics initially and after 2.5‐3 years were evaluated by a questionnaire to the patients physician and by non‐fasting C‐peptide. The study comprised patients registered 1983‐84, and for 281 patients (37%), complete information was obtained. At diagnosis 75% were classified as Type 1, 19% as Type 2, and 6% as secondary diabetes or as uncertain by their physician. Twenty patients (7.1%) were reported to have ketoacidosis. Seventy‐five percent were treated with insulin, 7% with oral hypoglycaemic agents (OHG), and 18% with diet alone. At follow‐up 71% were classified as Type 1, 21% as Type 2, and 8% as secondary or uncertain while treatment was 82% insulin, 8% OHG, and 9% diet. During the follow‐up period 42% of the initially non‐insulin‐treated patients were put on insulin whereas only a few stopped insulin treatment. Patients treated with diet or OHG at follow‐up were older, had higher percent desirable weight, and lower blood glucose at diagnosis than patients treated with insulin. All except one patient had measurable random C‐peptide at follow‐up and mean values were for patients treated with insulin 0.55, OHG 1.41 and diet alone 1.29 nmol I−1. Random blood glucose results were similar. In conclusion the majority of newly diagnosed patients in the age group 15–34 years have the characteristics of Type 1 diabetes and Type 2 diabetes is rare before 25–30 years of age. Patients with biochemically mild hyperglycaemia are difficult to classify and there is a need for new guidelines for classification of diabetes which include aetiopathogenetic aspects.

Islet antibodies and remaining beta-cell function 8 years after diagnosis of diabetes in young adults : a prospective follow-up of the nationwide Diabetes Incidence Study in Sweden.

Objectives.  To establish the prevalence of remaining β‐cell function 8 years after diagnosis of diabetes in young adults and relate the findings to islet antibodies at diagnosis and 8 years later.

Diabetes in hypertensive women: an effect of antihypertensive drugs or the hypertensive state per se?

A total of 226 women participating in a longitudinal study who were found to be hypertensive (initial values ≥160 mmHg for the systolic blood pressure and/or >95 mmHg for the diastolic blood pressure) were followed up with respect to the risk of developing diabetes during a 12‐year study period. For each year of follow‐up, information on whether each participant was taking antihypertensive drugs or not was collected. As a result there were 1339 ‘treatment years’ and 1449 ‘non‐treatment years’ of follow‐up. All 16 women who developed diabetes during the follow‐up period were taking antihypertensive drugs at the time of onset of their diabetes. A similar observation was made when 145 women within the upper age‐specific decentiles of systolic blood pressure were followed up in the same way. These results suggest that in hypertensive subjects antihypertensive drugs rather than the hypertensive state per se predispose to diabetes mellitus.

Diabetes incidence in users and non-users of antihypertensive drugs in relation to serum insulin, glucose tolerance and degree of adiposity : a 12-year prospective population study of women in Gothenburg, Sweden

Abstract. As part of a prospective population study in Gothenburg, Sweden, women aged 50 years were subjected to an intravenous glucose tolerance test on entry to the study and followed up for 12 years. Manifest diabetes was the only end‐point registered in this part of the study. Of 352 initially non‐diabetic women, 17 (4.8%) subjects developed diabetes, with a fourfold increased risk in women taking antihypertensive drugs (diuretics or β‐blockers, or both) compared with women who were not taking such medication. The increased risk was observed independently of initially measured glucose metabolism variables and degree of adiposity, although the incidences were higher overall if the use of antihypertensive drugs was combined with fasting hyperinsulinaemia and adiposity. This study provides further evidence to support the view that diuretics and β‐blockers are precipitators of type 2 diabetes mellitus.