Risto Pelkonen

Obstructive sleep apnoea syndrome in morbidly obese patients

Abstract. Twenty‐seven morbidly obese patients (13 men and 14 women) with body mass index ≥ 40 kg m−2 were examined. The mean age of the subjects was 36.9 ± 8.2 years (range 23–51 years), and the mean BMI was 50.2 ± 6.2 kg m−2 (range 40.0–62.9 kg m−2). A whole‐night sleep recording was made for all patients with signs or symptoms indicative of possible obstructive sleep apnoea syndrome (OSAS). If the first nocturnal sleep recording was abnormal, it was controlled after 1 year. Eleven (10 men and one woman) of the 27 patients had an oxygen desaturation index (ODI) of 10 h−1. They were symptomatic with excessive daytime sleepiness or other daytime symptoms of OSAS. The occurrence of OSAS in men and women was 76.9 and 7.1%, respectively. Arterial hypertension was associated with OSAS, but not with smoking or the degree of obesity. Antihypertensive treatment was received by nine of the 27 patients; six of them had OSAS. Thus six of the 11 (54.5%) patients with OSAS and three of the 16 (18.8%) nonapnoeic patients were treated for arterial hypertension (Fisher exact test, P = 0.042). The odds ratio of OSAS for arterial hypertension is 5.2 (95% CI, 0.71–43.6). Vertical‐banded gastroplasty was performed in 14 patients, three of whom had OSAS. The selection of patients for gastroplasty was made without taking into account the results of sleep recordings. In the three OSAS patients, a 30–38% reduction in BMI was achieved by surgery. Eight patients with OSAS were treated with an intensified dietary regimen, and the reduction in BMI ranged from –2.6 to 33%. OSAS was either cured or significantly improved in six (55%) patients, with a mean reduction in BMI of 27%, while in patients with persistent OSAS the mean reduction in BMI was only 7%.

secondary Failure to Treatment with Oral Antidiabetic Agents in Non-insulin-dependent Diabetes

To study the etiopathogenesis of secondary drug failure to treatment with oral antidiabetic agents in patients with non-insulin-dependent diabetes (NIDD) we compared 60 “nonresponders” with 60 “responders” to treatment with oral drugs. Secondary drug failure was defined as mean diurnal blood glucose >12 mmol/L after an initial good response of ≥2 yr. The nonresponders were characterized by 50% lower C-peptide concentrations than the responders (P < 0.001). We could not, however, define a critical C-peptide level to discriminate between patients requiring and not requiring insulin therapy. There was a wide overlap of individual C-peptide values between responders and nonresponders that attenuates the clinical value of single C-peptide measurements in predicting therapy. Only by serial measurements over a period of time was it possible to achieve information about changes in beta cell function. The nonresponders showed increased frequency of islet cell (P < 0.01), thyroid antimicrosomal (P < 0.01), and gastric parietal cell antibodies (P < 0.02). In nonresponders, HLA-antigen B8 was increased (P < 0.05) and HLA-B7 decreased (P < 0.01) compared with frequencies of responders. In conclusion, impaired beta cell function is a characteristic feature of many, but not all, NIDD patients who fail on treatment with oral antidiabetic drugs. The presence of islet cell and thyrogastric antibodies can unmask a distinct group of NIDD patients with a high risk of secondary drug failure and subsequent insulin dependency. HLA typing may further help to predict secondary failure in NIDD.

Effect of Interferon on Glucose Tolerance and Insulin Sensitivity

Many viral infections induce interferon (IFN) production and cause insulin resistance. To examine the causal relationship between IFN and insulin resistance, we injected natural human leukocyte IFN-α (3 × 106 IU, i.m.) twice overnight in eight healthy subjects and determined oral (OGT) and intravenous (IVGT) glucose tolerance and sensitivity to insulin (287 nmol or 40 mU · m−2 · min−1 euglycemic insulin clamp) the following morning. IFN caused mild influenzalike symptoms and induced a rise in circulating glucose, insulin, hydrocortisone (cortisol), growth hormone, and glucagon concentrations (P < .05–.001). In the OGT test, the area under the glucose curve was 2.6-fold greater (P < .02), and the disappearance rate of intravenously administered glucose was reduced by 28% (P < .05) after IFN administration. The impairment in OGT and IVGT occurred despite augmented insulin response. Insulin-stimulated glucose disposal was reduced by 22% (P < .005), and insulin clearance increased by 18% (P < .02) after IFN administration. When the insulin-clamp study was repeated in patients with steady-state hyperinsulinemia that was 12% higher (P < .005) after IFN, the glucose disposal rate was still reduced by 15% (P < .01). These data indicate that IFN 1) stimulates counterregulatory hormone secretion, 2) impairs glucose tolerance and insulin sensitivity, and 3) stimulates insulin clearance. Thus, IFN may be involved in the development of insulin resistance during viral infections.

Serum lipids in acromegaly

Serum cholesterol and triglyceride concentrations were determined in 46 patients with active acromegaly but with otherwise intact pituitary function. The mean serum-cholesterol level of the patients was lower and the mean serum-triglyceride higher than in the basic population of comparable age. The incidence of hypercholesterolemia was similar to that in general population, whereas the incidence of type IV hypertriglyceridemia was almost three times higher than in control population. The serum triglyceride level was not related to relative body weight, basal serum growth hormone, or insulin concentrations, nor did it correlate with glucose tolerance or with plasma-insulin response to oral glucose. However, the patients with highest plasma-insulin response had significantly higher serum triglyceride than the rest of the acromegalic group. The endogenous serum-triglyceride turnover rate showed no consistent changes, but increased serum triglyceride was associated with increased production rate. Upon successful surgical treatment of the acromegaly, serum-triglyceride level decreased in most of the cases who initially had hypertriglyceridemia. It is concluded that acromeagaly can give rise to moderate secondary hypertriglyceridemia.

Pathogenesis and Prevention of the Dawn Phenomenon in Diabetic Patients Treated with CSII

The mechanism of the dawn phenomenon was studied in 12 C-peptide-negative type I diabetic patients (age 30 ± 2 yr) treated with continuous subcutaneous insulin infusion. During constant basal infusion, nocturnal glycemia remained constant until 4 a.m., but began to rise thereafter in 10/12 patients, with the mean rise from 4.6 ± 0.4 mmol/L to 6.1 ± 0.7 mmol/L (P < 0.01) by 8 a.m. In these patients the rate of glucose production (Ra, 2.14 ± 0.04 mg/kg/min, 3-H3-glucose infusion) exceeded the rate of utilization (Rd, 1.89 ± 0.03 mg/kg/ min, P < 0.02). When the patients were restudied after the infusion rate was increased by 49 ± 7%, Ra fell to 1.75 ± 0.03 mg/kg/min (P < 0.01) and the dawn phenomenon was abolished. However, both Ra and Rd remained higher in the diabetic subjects (P / 0.05) than in eight healthy control subjects, in whom Ra (1.66 ± 0.02 mg/kg/min) was equal to Rd with glycemia remaining unchanged. Peripheral free insulin levels in the diabetic patients were similar during constant (12.3 ± 0.5 mU/L) and increased infusion rate (11.3 ± 0.4 mU/L), and higher than those of the control subjects (5.2 ± 0.2 mU/L, P < 0.05). A diurnal rise in serum cortisol levels occurred 1 h earlier in the diabetic than in the control subjects, and Ra was directly proportional to serum cortisol concentration (r = 0.61; P < 0.01). Serum growth hormone levels were also slightly higher in the diabetic than the control subjects. In conclusion: (1) A dawn phenomenon is associated with an excessive rate of glucose production, rather than impaired utilization; (2) this may be explained, at least in part, by elevated counterregulatory hormone levels; and (3) a step-up in the overnight insulin delivery reduces hepatic glucose production and so prevents the dawn phenomenon.

Effect of acute elevation of plasma glycerol, triglyceride and FFA levels on glucose utilization and plasma insulin.

The effects of raised plasma levels of glycerol, free fatty acids (FFA) and triglyceride on the disappearance rate (Kg) of intravenously administered glucose (25 gm.) and on the response of plasma immunoreactive insulin (IRI) to intravenous glucose were studied in thirty-six subjects. Increase of plasma glycerol level by oral glycerol augmented the Kg but not the glucose-stimulated plasma insulin level. Alimentary hyperglyceridemia enhanced the disappearance rate of glucose and the response of plasma insulin to glucose. Heparin injected intravenously during alimentary glyceridemia caused a five-to seven-fold increment of the levels of plasma FFA and glycerol but did not influence either the disappearance rate of glucose or the response of plasma insulin to glucose. Heparin injected in fasting state slowed significantly the disappearance rate of glucose, but did not change the insulin response.

SLEEP APNOEA AND DAYTIME SLEEPINESS IN ACROMEGALY: RELATIONSHIP TO ENDOCRINOLOGICAL FACTORS

Sleep history and pituitary function were studied and sleep polygraphy performed in 11 acromegalic patients before and after pituitary surgery. Excessive daytime sleepiness or habitual snoring or both together, as well as an elevated fasting level of serum GH occurred in all the patients. In five men but in none of the women an abnormal number of episodes of sleep apnoea were observed. Pituitary adenomectomy improved the apnoea frequency in one patient, whereas in the others the abnormality was still present 1 year later. After operation the fasting level of serum GH became normal in eight patients, two of them with persisting sleep apnoea. The sleep apnoea syndrome is common and clinically important in acromegaly. Its early diagnosis using polygraphic monitoring is emphasized, as it is a treatable disorder.

Alcohol With a Meal Has No Adverse Effects on Postprandial Glucose Homeostasis in Diabetic Patients

OBJECTIVE To examine the effect of moderate alcohol intake with a meal on gluco e homeostasis in diabetic patients. RESEARCH DESIGN AND METHODS Alcohol (1 g/kg, an aperitif before, wine during, and a drink after a meal) or an equal amount of mineral water was given during a dinner. Blood glucose and insulin concentrations were measured before, uring, and after the meal until the next morning. This study was conducted at the Helsinki University Hospital Metabolic Ward and the Finnish Diabetes Association Education Center. The participants in the study included 10 type I diabetic patients treated with insulin and 16 type II diabetic patients treated with diet alone or with diet and oral drugs. In each subject, we examined hypoglycemic episodes or differences in blood glucose or serum insulin concentrations between alcohol and the control study. RESULTS In type I diabetic patients, blood glucose and insulin concentrations were virtually identical in both studies. In type II diabetic patients, alcohol slightly enhanced the meal-induced insulin secretion resulting in lower blood glucose concentrations next morning. No hypoglycemic glucose concentrations were observed in either group after alcohol ingestion. CONCLUSIONS Moderate alcohol intake with a meal does not lead to hypo- or hyperglycemia in diabetic patients.

Is the treatment of metastatic carcinoid tumor with interferon not as successful as suggested

Eight patients with metastatic carcinoid tumor, seven of whom had symptoms of the carcinoid syndrome, were treated with either human leukocyte interferon (seven patients) or recombinant alpha‐interferon (IFN alpha‐2b) (one patient) at doses of 4.5 to 21 × 106 IU weekly for 1 to 21 (mean, 8.5) months. Tumor regression on computed tomography (CT) scan was found in one patient, the CT findings remained unchanged in three, and the tumor progressed in four patients. A clearcut and continuing decrease in urinary levels of 5‐hydroxyindoleacetic acid (5‐HIAA) was observed in one patient and a transient one in four patients. The symptoms improved in only two of seven patients. Four patients had leukopenia develop, which was circumvented by reducing the dose. The authors conclude that interferon therapy of the carcinoid tumor is not as successful as has been suggested in previous reports.

Testosterone‐secreting virilizing adrenal adenoma with human chorionic gonadotrophin receptors and 21‐hydroxylase deficiency

A 60‐year‐old woman was evaluated for persistently elevated serum testosterone concentrations after bilateral ovariectomy. Her serum cortisol, androstenedione, dehydroepiandrosterone sulphate and 17‐hydroxyprogesterone levels were normal, and decreased after dexamethasone administration. Those of testosterone (17.8–18.4 nmol/l) were remarkably high (normal range 0.7–2.8 nmol/l), were not suppressed by dexamethasone, but clearly increased after hCG administration (up to 128 nmol/l). Computed tomography revealed an adenoma in the right adrenal gland and adrenal scintigraphy under dexamethasone suppression visualized this adenoma. A right adrenalectomy was performed. (1) The tumour was histologically and ultrastructurally adrenocortical adenoma of zona reticularis cell type. (2) The adenoma tissue contained hCG receptors (198 fmol/g). (3) During tissue culture both ACTH and hCG were capable of maintaining its testosterone production, which was attenuated with time without stimulation. (4) The adenoma tissue did not elaborate 21‐hydroxylated steroids In contrast to normal adrenal tissue. Thus the aberrant endocrine behaviour of this gonadotrophin‐responsive testosterone‐secreting adenoma of adrenal zona reticularis cell origin can be explained by ectopic functional hCG receptors and the lack of 21‐hydroxylase activity