Serum calcium: a new, independent, prospective risk factor for myocardial infarction in middle-aged men followed for 18 years.

BACKGROUND: Primary hyperparathyroidism (HPT) is a disease characterized by hypercalcemia, and associated with an increased mortality in cardiovascular diseases. However, serum calcium levels within the normal range have not been evaluated as a prospective cardiovascular risk factor. METHODS: A cohort of males aged 50 (n = 2183) were investigated in 1970-1973 for serum calcium and known cardiovascular risk factors. They were then followed up over the next 18 years. RESULTS: During the follow-up period, 180 subjects experienced a myocardial infarction (MI). The serum calcium levels were significantly elevated at the baseline (2.37 +/- 0.09 SD versus 2.35 +/- 0.09 mmol/l, p < 0.03) in the subjects who developed a MI when compared with the rest of the cohort. Also blood pressure, body mass index (BMI), fasting insulin, serum cholesterol, serum triglycerides, and the atherogenic index were significantly elevated in the MI group (p < 0.01), while HDL-cholesterol was lower at the baseline investigation (p < 0.01). Cox's proportional hazard analysis showed that only serum calcium (p < 0.01), BMI (p < 0.0003), diastolic blood pressure (p < 0.0009), and the atherogenic index (p < 0.002) were significantly independent risk factors for MI. The range of serum calcium levels from the mean value, -2 SDs to the mean value +2 SDs corresponds to a variation in estimated risk for MI ranging from 0.06 to 0.15. CONCLUSIONS: Serum calcium was found to be an independent, prospective risk factor for MI in middle-aged males suggesting a role for extracellular calcium levels in the atherosclerotic process.

The risk to develop NIDDM is related to the fatty acid composition of the serum cholesterol esters.

This investigation was undertaken to study whether the risk to develop non-insulin-dependent diabetes mellitus (NIDDM) among 50-year-old men during a 10-year follow-up period was related to the fatty acid composition of their serum cholesterol esters. There were highly significant differences in the initial health survey between the fatty acid composition in serum in subjects who remained normoglycemic (n = 1,753) and in those who later developed NIDDM (n = 75). The main differences were that the latter had higher proportions of saturated fatty acids and palmitoleic acid (16:1 omega-7), a low proportion of linoleic acid (18:2 omega-6), and a relatively high content of gamma-linolenic (18:3 omega-6) and dihomo-gamma-linolenic (20:3 omega-6) acids in the serum cholesterol esters. The picture was similar also after adjusting for differences in body mass index. In a logistic model, a high proportion of dihomo-gamma-linolenic acid remained a significant contributor to the development of diabetes, along with the height of the insulin index, the blood glucose concentration at 60 min, and the fasting insulin concentration. The increased risk to develop NIDDM related to the serum cholesterol ester fatty acid composition may be mediated by diet and/or genetic factors.

Risk factors for developing non-insulin dependent diabetes: a 10 year follow up of men in Uppsala.

OBJECTIVE: To analyse anthropometric and metabolic characteristics as risk factors for development of non-insulin dependent diabetes mellitus in middle aged normoglycaemic men. DESIGN: Prospective population study based on data collected in a health survey and follow up 10 years later. SETTING: Uppsala, a middle sized city in Sweden. SUBJECTS: 2322 men aged 47-53, of whom 1860 attended the follow up 7-14 years later, at which time they were aged 56-64. MAIN OUTCOME MEASURES: Incidence of non-insulin dependent diabetes. RESULTS: In a multivariate logistic regression analysis, variations of 1 SD from the mean of the group that remained euglycaemic were used to calculate odds ratios and 95% confidence intervals. Blood glucose concentration 60 minutes after the start of an intravenous glucose tolerance test (odds ratio = 5.93, 95% confidence interval 3.05 to 11.5), fasting serum insulin concentration (2.12, 1.54 to 2.93), acute insulin increment at an intravenous glucose tolerance test (1.71, 1.21 to 2.43), body mass index (1.41, 1.01 to 1.97), and systolic blood pressure (1.23, 0.97 to 1.56) were independent predictors of diabetes. In addition, the use of antihypertensive drugs at follow up (selective or unselective beta blocking agents, thiazides, or hydralazine) was an independent risk factor (1.70, 1.11 to 2.60). CONCLUSIONS: Metabolic and anthropometric characteristics associated with or reflecting insulin resistance as well as a poor acute insulin response to glucose challenge were important predictors of future diabetes in middle aged men. Antihypertensive drugs were found to constitute a further, iatrogenic risk factor.

Risk factors for the development of hypertension: a 10-year longitudinal study in middle-aged men.

A group of middle-aged men (n = 2322) were examined at a health screening which included an intravenous glucose tolerance test (IVGTT) with insulin determinations, and were then re-examined approximately 10 years later. At the first survey, 19.6% of the participants had hypertension, defined as diastolic blood pressure greater than or equal to 95 mmHg or were receiving drug treatment for hypertension. At follow-up survey, the corresponding figure was 34.7%. Baseline blood pressures were the strongest predictors of future development of hypertension. In the absence of baseline blood pressures, fasting and late insulin levels at IVGTT, difference in body mass index between the surveys and heredity for hypertension were significant risk factors for hypertension. When a difference in diastolic blood pressure was used as an independent variable, the only significant risk factor was the difference in body mass index. Thus, insulin resistance (as reflected by fasting, late insulin levels and body mass index) seems to be related to the development of hypertension.

Do antihypertensive drugs precipitate diabetes in predisposed men?

OBJECTIVE: To evaluate the influence of antihypertensive treatment and metabolic characteristics on the development of diabetes mellitus in middle aged men. DESIGN: Prospective study over an average of nine years. SETTING: Community based health survey of middle aged men carried out at the University of Uppsala. SUBJECTS: Seventy three hypertensive men aged 49-54 and 65 normotensive controls matched for body mass index, glucose disappearance rate (k value) at an intravenous glucose tolerance test, and serum triglyceride and cholesterol concentrations. INTERVENTIONS: Hypertensive group was treated with beta blockers, thiazides, hydralazine, or combinations of these drugs. Treatment was not randomised. MEASUREMENTS AND MAIN RESULTS: Intravenous glucose tolerance, fasting blood glucose and serum lipid and insulin concentrations, body weight and height, three skinfold measurements, and blood pressure were recorded both during an initial health screening survey in 1970-3 and at a follow up survey in 1980-3. In the period between the two surveys 12 hypertensive men and two controls developed diabetes. Review of values obtained at the initial survey showed that the hypertensive men who developed diabetes or impaired glucose tolerance could be distinguished from those hypertensive men who did not by virtue of a higher fasting serum insulin concentration (26.1 v 15.2 mU/l (confidence interval of difference -15.2 to -6.2)), a lower peak serum insulin concentration (78.9 v 94.3 mU/l (confidence interval of difference -1.1 to 41.1)), and a lower k value (1.29 v 1.68 (confidence interval of difference -0.02 to 0.68)). The insulin index (peak insulin concentration divided by fasting insulin concentration), however, decreased significantly in the hypertensive men over time irrespective of whether they developed diabetes but did not change in the controls. Furthermore, the serum triglyceride concentration increased in the treated group and decreased in the controls. CONCLUSION: A severalfold difference in the incidence of diabetes between treated hypertensive and non-treated, normotensive men may be a consequence of the treatment, which may be particularly deleterious in men predisposed to diabetes.

Increase in serum parathyroid hormone levels after prolonged physical exercise.

Serum concentrations of parathyroid hormone (PTH), calcium, magnesium, phosphate and myoglobin were measured regularly during a 5-d recovery period in 17 men who had participated in a 7-d field exercise maneuver with intense physical activity. Immediately after the exercise, there was an increase in serum PTH levels of the same magnitude as the maximal rise during a hypocalcemic test. The rise in PTH was not related to changes in serum electrolytes, but was significantly correlated to an increase in serum myoglobin, indicating that those who performed the largest amount of work also experienced the greatest stimulus for secretion of PTH. There were no significant changes of the serum total calcium and only a small initial rise of the magnesium concentrations. Serum phosphate levels were greatly reduced and gradually returned during recovery. This study extends previous observations, from short-term investigations, that physical activity stimulates secretion of PTH.

Reduction of blood pressure by treatment with alphacalcidol. A double-blind, placebo-controlled study in subjects with impaired glucose tolerance.

Disturbances of calcium or vitamin D metabolism have been suggested to be of pathogenetic importance both for hypertension and impaired glucose tolerance, two disorders that are commonly associated. In the present study 65 men, aged 61-65 years, with impaired glucose tolerance were enrolled in a prospective, double-blind, placebo-controlled study over 12 weeks evaluating the effects of 0.75 microgram alphacalcidol, a synthetic analog to the active metabolite of vitamin D. In the 26 patients with blood pressure greater than or equal to 150/90 mmHg before treatment a significant reduction (p less than 0.01) of both the systolic (SBP) and diastolic (DBP) blood pressure was found after therapy (from 171/95 to 150/88 mmHg). The effect was additive to concomitant antihypertensive treatment and was correlated (p = 0.03) to a reduction of serum levels of parathyroid hormone. Also in the whole group of patients given alphacalcidol blood pressure was moderately lowered from a mean of 152/87 +/- 22/10 (SD) to 143/84 +/- 17/8 mmHg. There were no relationships between the changes in body weight, blood glucose or insulin parameters and the changes in blood pressure during the trial. The findings are compatible with the concept that calcium metabolism influences blood pressure regulation and suggest that supplementation with a physiologic dose of active vitamin D could be beneficial for patients with high blood pressure.

Physical training as treatment for type 2 (non-insulin-dependent) diabetes in elderly men. A feasibility study over 2 years.

At a health examination of men approximately 60 years old, 48 were found to have Type 2 (non-insulin-dependent) diabetes. All had been healthy 10 years earlier. The intention was to randomly allocate those with mild diabetes to a training or a control group and study the long-term influence of regular training on the progress of the disease. However, it was found that the majority--39 of 48--had other diseases or were on treatment which made regular training difficult and would have complicated the interpretation of the metabolic effects of training. Eight men took part in a physical training programme for up to 2 years. Aerobic capacity, glucose tolerance and serum lipoproteins were measured before and at the end of the training period. Another group of eight men with Type 2 diabetes, of similar weight, age and relative aerobic capacity, who did not undergo the physical training, served as control subjects. The oxygen uptake increased by 16% in the training group and decreased by 12% in the control group but no significant changes could be demonstrated in body weight, fasting blood glucose, serum lipoproteins, glucose tolerance or insulin values at a 75-g oral glucose tolerance test between the two groups. Two patients in the training group developed coronary heart disease, two deteriorated metabolically (drug treatment had to be added), and there were two drop-outs. The results cast doubts on the feasibility and efficacy of physical training as a long-term treatment for the majority of Type 2 diabetic patients, who are older than 60 years.

Prevalence of renal stones in 60-year-old men. A 10-year follow-up study of a health survey.

Information on the occurrence of renal stones was obtained in a health survey of 50-year-old men and at follow-up of the same group 10 years later. At the latter investigation, 338 of 1781 participants (19%) had a history of renal stone formation. In 47% there had been recurrences. For the individual there was a continuous risk of acquiring a first renal stone up to the age of 60. Approximately 0.5% of the entire unselected population experienced onset annually up to this age. Recurrent renal stones occurred primarily in those with a positive family history of stones or early onset of stones, as well as in those who previously had frequently formed stones. A carefully obtained clinical history should be useful in predicting recurrences in the individual stone former.

Treatment with one-alpha-hydroxycholecalciferol in middle-aged men with impaired glucose tolerance--a prospective randomized double-blind study.

Experimental evidence suggests a specific role for the active metabolite of vitamin D (1,25(OH)2D3) in insulin secretion. In order to evaluate the possible clinical significance, 65 middle-aged men with impaired glucose tolerance, and normal serum levels of vitamin D metabolites, were enrolled in a three-month study where they were given either 0.75 micrograms alpha-calcidol (1 alpha(OH)D3) daily or placebo. Indices of glucose and lipid metabolism were evaluated before and after treatment. There were no significant changes during the trial neither for fasting blood glucose, hemoglobin A1c or for the intravenous glucose tolerance between the treatment and the placebo groups, nor were there any consistent changes in insulin values during the glucose tolerance test. Subjects treated with alpha-calcidol displayed a significant reduction in body weight with an average of 1.1 kg, while those receiving placebo lost no weight. Treatment did not affect the serum lipoprotein values. Thus, a modest dose of active vitamin D, which did not cause elevation of serum calcium, did not provide general improvement of glucose tolerance or of insulin secretion when given to patients with impaired glucose tolerance, but without vitamin D deficiency, over a three-month period.

Insulin receptor binding and metabolic effects of insulin in human subcutaneous adipose tissue in untreated non-insulin dependent diabetes mellitus.

Insulin action at the target tissue level in non-insulin dependent diabetes mellitus was investigated using human adipose tissue. Specific adipocyte receptor binding of insulin and the effects of the hormone on glucose oxidation and lipolysis were determined in subcutaneous adipose tissue. The study included 25 patients with untreated non-insulin dependent diabetes mellitus and 38 healthy control subjects matched for age, sex and body weight. Insulin stimulated adipose tissue glucose oxidation in a dose-dependent way in the control subjects. On the other hand, a marked inhibition of this insulin effect was observed in the diabetics. A weak stimulation was observed only at high unphysiological hormone concentrations [greater than or equal to 0.7 nmol/l] and the maximal insulin response was 6 times lower than that in the control subjects. However, neither specific insulin receptor binding nor the antilipolytic effect of insulin were inhibited in diabetes. Similar results with insulin binding and the metabolic effects of insulin were obtained in non-obese normoinsulinemic diabetics as compared to moderately obese hyperinsulinemic diabetics. It is concluded that adipose tissue insulin resistance in non-insulin dependent diabetes mellitus only involves glucose metabolism and not antilipolysis. Furthermore, it may solely be due to postreceptor defects in insulin action and seems not to be influenced by obesity or oversecretion of insulin.

Effects of obesity, hyperinsulinemia, and glucose intolerance on insulin action in adipose tissue of sixty-year-old men.

The relative effects of obesity alone, and in combination with fasting hyperinsulinemia and glucose intolerance, on the peripheral action of insulin in adipose tissue were investigated in twenty-four 60-yr-old men, who had been followed for 10 yr. They were divided into four groups of six subjects each on the basis of the following criteria: (1) normal body weight, normal fasting insulin level, and normal glucose tolerance; (2) moderate obesity, normal fasting insulin level, and normal glucose tolerance; (3) moderate obesity, fasting hyperinsulinemia, and normal glucose tolerance; and (4) moderate obesity, fasting hyperinsulinemia, and newly developed, moderate, untreated fasting hyperglycemia and/or glucose intolerance (i.e., mild type II diabetes mellitus). Specific adipocyte insulin binding and the effects of the hormone on adipose tissue lipolysis and glucose oxidation were determined. Insulin receptor binding per cell and per cell surface area were similar in all four groups. Regarding antilipolysis, the insulin sensitivity was the same in all groups and the maximum effect was significantly increased in the three obese groups, as compared with the normal-weight control group. In groups 1-3, insulin stimulated adipose tissue glucose oxidation in a dose-dependent way, and the sensitivity and responsiveness to insulin were comparable. In contrast, in the obese glucose-intolerant subjects (4) there was no significant effect of insulin on glucose oxidation when the hormone was added in increasing concentrations of less than or equal to 35 nmol/L. The basal glucose oxidation was similar in all four study groups. The in vivo insulin tolerance was gradually reduced in groups 2-4, as compared with the normal-weight control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Findings at a re-examination of a self-administered questionnaire after two and a half years in a sample of sixty-year-old men.

The result of examinations conducted by self-administered questionnaire on two occasions almost three years apart in the same sample of men in their sixties is related. An overall consistency of 87% was found, but the proportion of changed answers differed from 7 to 26% among the nine sections of the questionnaire, the highest rate of change occurring in the section on physical habits. Most changes could be anticipated among men in their seventh decade, the rise in knowledge about cardiovascular diseases among relatives being an exception.