Adrenocorticotropin-independent Cushing's syndrome in pregnancy related to overexpression of adrenal luteinizing hormone/human chorionic gonadotropin receptors.

Cushing's syndrome during pregnancy is rare, and rather than being of pituitary origin most patients exhibit ACTH-independent adrenal hypercortisolism. In some cases the syndrome has spontaneously resolved post partum, suggesting the presence of a pregnancy-associated stimulatory factor(s). We describe a case with aberrant adrenal LH/hCG receptors in a large adrenal tumor as a possible explanation for cortisol hypersecretion and tumor growth in Cushing s syndrome during pregnancy. A 27-yr-old woman presented with hypertension and diabetes mellitus in early pregnancy. Investigations revealed hypercortisolemia, suppressed ACTH-levels, and a 6.4- cm right adrenal tumor. The tumor was successfully removed by laparoscopy at 26th week of pregnancy. Hypercortisolism and hypertension resolved post-operatively. The tumor displayed higher LH/hCG receptor mRNA and protein positivity than adjacent normal adrenal tissue as examined by in situ hybridization and immunocytochemistry. High physiological levels of hCG, in conjunction with aberrant adrenal LH/hCG receptor overexpression, may have contributed to the development of Cushing's syndrome in pregnancy.

Continuous Subcutaneous Glucose Monitoring System in diabetic mothers during labour and postnatal glucose adaptation of their infants.

AIMS: To assess a new technique for continuous monitoring of glucose concentration during labour in diabetic mothers. A second objective was to study maternal glucose levels in relation to postnatal glucose adaptation and the need for intravenous (IV) glucose treatment in the newborn infant. METHODS: Fifteen pregnant women with insulin-treated diabetes mellitus participated in this prospective pilot study. To measure their glucose control during labour we used the Continuous Subcutaneous Glucose Monitoring System (CGMS; Medtronic, Minneapolis, MN, USA) to calculate the mean glucose concentration and the area under the curve (AUC) in the last 120 min before delivery. All infants of these women were transferred to the neonatal care unit for early oral feeding and blood glucose measurements up to 14 h after delivery. Infants received IV glucose if blood glucose values were repeatedly < 2.2 mmol/l. RESULTS: All women coped well with the CGMS monitoring. AUC 0-120 min before delivery, mean glucose concentration 0-120 min before delivery and cord plasma insulin level were all significantly associated with the need for IV glucose in the newborn children. CONCLUSIONS: In this study we found an association between maternal glucose concentrations during labour and postnatal glucose adaptation and need for IV glucose treatment in the infants. Online monitoring of glucose levels during delivery might help us to achieve maternal normoglycaemia and further reduce the risk of postnatal hypoglycaemia in the offspring.

Body composition in young female adults with Type 1 diabetes mellitus. A prospective case-control study.

AIMS: Overweight is common during late puberty in female patients with Type 1 diabetes. The aim of this study was to examine the change in body composition from late puberty to early adulthood in such female patients in comparison with age-matched control subjects. METHODS: Eighteen females with Type 1 diabetes and 19 healthy female control subjects were recruited for a case-control study at the age of 16-19 years (baseline). Six years later, 16 of the diabetic females and 17 of the control subjects were re-examined (follow-up). Body composition was assessed by dual energy X-ray absorptiometry. RESULTS: Body mass index (BMI) and fat mass index (total fat mass/height2) were significantly higher at baseline in the diabetic patients than in the control subjects (26.4 +/- 2.6 vs. 23.9 +/- 3.7 kg/m2, P < 0.05, and 10.0 +/- 2.4 vs. 8.0 +/- 2.8 kg/m2, P = 0.04, respectively). At follow-up, these parameters still tended to be higher in the diabetic group (27.8 +/- 4.9 vs. 24.6 +/- 5.7 kg/m2, P = 0.09, and 11.8 +/- 5.6 vs. 8.7 +/- 4.9 kg/m2, P = 0.05, respectively). BMI at baseline was strongly correlated to BMI at follow-up in both diabetic patients (r = 0.60; P < 0.05) and control subjects (r = 0.83; P < 0.01). CONCLUSIONS: Increased fat mass in pubertal girls with Type 1 diabetes seems to persist in young adulthood. This study emphasizes the need for new strategies to prevent the development of overweight during puberty in diabetic girls.

Body composition and bone mineral density in long-standing type 1 diabetes.

OBJECTIVES: To study body composition and bone mineral density (BMD) in adult patients with long-standing type 1 diabetes mellitus. RESEARCH DESIGN AND METHODS: In a population-based study, body composition and BMD were evaluated by dual energy X-ray absorptiometry in 38 patients with type 1 diabetes since childhood, compared with 38 age- and sex-matched controls. The mean age was 43 years (range 33-55 years) and the mean duration of diabetes was 33 years (range 28-37 years). RESULTS: Besides a tendency to a reduced abdominal fat mass in diabetic males, no difference was observed in fat mass, muscle mass, or BMD between the groups. Significant correlations were found between insulin dosage and whole body fat mass in diabetic females and between serum cholesterol levels and abdominal fat mass in diabetic males. CONCLUSION: Patients with long-standing type 1 diabetes with onset in childhood and adolescence seem to show only minor differences in body composition and no difference in BMD compared with closely matched healthy controls.

Body composition in adolescent girls with type 1 diabetes.

AIMS: To compare body composition in adolescent girls with Type 1 diabetes with healthy controls. RESEARCH DESIGN AND METHODS: In this population-based study, body composition was examined, using dual-energy X-ray absorptiometry (DXA) and skinfold measurements, in 18 adolescent post-menarcheal females, 16-19 years of age, with Type 1 diabetes since childhood in comparison to age-matched healthy control subjects. RESULTS: Body mass index was 2.7 kg/m2 higher in diabetic patients (26.3 +/- 2.6 vs. 23.6 +/- 3.8; P < 0.05). The overweight consisted almost entirely of increased fat mass, as evaluated by both skinfold measurements and DXA. Bone mineral density did not differ between the two groups. In diabetic females, the distribution of the fat mass was increased in the upper part of the body. The fat distribution, expressed as the abdominal-to-leg ratio, was significantly correlated to glycated haemoglobin (HbA1c) (r = 0.69; P < 0.005), daily dosage of insulin expressed per kilogram body weight (r = 0.78; P < 0.0005) and total cholesterol (r = 0.60; P < 0.001). CONCLUSIONS: The observed overweight in adolescent females with Type 1 diabetes is explained by an increased fat mass. Abdominal fat accumulation was associated with poor glycaemic control, increased need for insulin and elevated blood lipids.

Factors predicting clinical remission in adult patients with type 1 diabetes.

OBJECTIVES: To describe the course of clinical remission in adult patients (16-50 years of age) with type 1 diabetes and to identify factors predictive of the occurrence and length of remission. DESIGN: A retrospective cohort study. SUBJECTS: Sixty-two consecutive patients (43 men and 19 women) with new onset IDDM, 27 +/- 8 years at diagnosis and treated with multiple insulin injections from the beginning. SETTING: Department of Medicine, Uppsala University Hospital and Orebro Medical Centre, Sweden. MAIN OUTCOME MEASURES: Length and occurrence of remission (defined as maintenance of HbA1c < or = 6.5% and an insulin dosage of < or = 0.4 U kg-1 day-1 for a minimum of 1 month) in relation to nine biochemical and clinical factors at diagnosis. RESULTS: Sixty-one per cent of the patients entered remission. The duration of remission was longer in males than females (10 +/- 12 vs. 2 +/- 3 months; P < 0.01). Male gender, normal serum bicarbonate at onset and a short time of classic symptoms before onset were predictive markers (P < 0.01; P < 0.05 and P < 0.01, respectively) for longer duration of remission. Low serum bicarbonate levels at onset were associated with lower occurrence of remission. Blood glucose, body mass index (BMI), and age at diagnosis did not influence the occurrence or the duration of remission. CONCLUSIONS: In most adult patients with new onset of type 1 diabetes remission is induced when using multiple insulin injection therapy. Male patients seem particularly prone to remission, and the length and extent of beta-cell strain prior to diagnosis strongly influences its course.

Prevalence of urinary tract symptoms in long-standing type 1 diabetes mellitus.

The purpose of this study was to evaluate the prevalence of urinary tract symptoms in a population-based cohort of 109 young adult patients with Type 1 diabetes mellitus with onset at < 16 years versus 208 sex- and age-matched controls. A validated postal questionnaire was used (response rate 87.2% in diabetic patients vs 77.4% in controls). Diabetic female patients had been treated more often than controls with antibiotics for urinary tract infections (UTI): 35/48 and 39/82 respectively; p < 0.01. Diabetic female patients with HbA1c > 9.0% did not have significantly more treated UTIs than those with HbA1c < or = 9.0%. Diabetic female patients had more social problems than controls in daily life because of urinary tract problems (11/48 and 3/82 respectively; p < 0.005) and used clamps to prevent wetting more often than did controls (5/48 vs 1/82, p < 0.05), whereas diabetic male patients never used condoms to prevent wetting. In conclusion, female but not male diabetic patients with long-standing Type 1 diabetes mellitus had increased frequency of treated UTIs. Urinary tract problems also interfered with normal social activities in female diabetic patients who had a greater need for clamps to prevent wetting.

Accelerated gastric emptying during hypoglycaemia is not associated with changes in plasma motilin levels.

This study examined whether or not changes in plasma concentrations of motilin and other gastrointestinal hormones known to affect gastric motility are associated with the accelerated gastric emptying seen during hypoglycaemia. While studying gastric emptying by scintigraphy in eight healthy subjects, the plasma concentrations of glucagon, adrenaline, motilin, gastrin, neuropeptide Y and somatostatin were measured during normoglycaemia and hypoglycaemia with simultaneous infusion of either atropine or saline. Blood glucose concentrations were checked by an insulin-glucose clamp. The plasma levels of glucagon and adrenaline increased markedly during both hypoglycaemic examinations compared with normoglycaemia. Neither motilin nor any of the other hormones displayed considerable changes during hypoglycaemia with and without atropine compared with normoglycaemia. No further information about the mechanisms behind the accelerated gastric emptying rate during hypoglycaemia was obtained by analysing motilin and the other gastrointestinal hormones.

Physiological hyperglycemia slows gastric emptying in normal subjects and patients with insulin-dependent diabetes mellitus.

BACKGROUND & AIMS: Marked hyperglycemia slows and hypoglycemia accelerates gastric emptying. The aim of this study was to determine the effect of physiological changes in blood glucose gastric emptying. METHODS: In 8 healthy subjects and 9 patients with insulin-dependent diabetes mellitus (IDDM) without gastrointestinal tract symptoms or evidence of neuropathy, gastric emptying of a mixed meal was measured by scintigraphy. Using an insulin-glucose clamp, the blood glucose concentration was stabilized at 4 and 8 mmol/L on 2 separate days. RESULTS: The intragastric retention of the solid meal component at 100 minutes was 55.2% +/- 4.5% at 8 mmol/L vs. 36.7% +/- 5.5% at 4 mmol/L (P = 0.004) in normal subjects and 44.2% +/- 4.2% vs. 35.7% +/- 4.2% (P = 0.004) in patients with IDDM. The time taken for 50% emptying of the liquid meal was 57.0 +/- 10.8 minutes at 8 mmol/L vs. 32.2 +/- 12.6 minutes at 4 mmol/L (P = 0.002) in normal subjects and 41.3 +/- 3.4 minutes vs. 29.1 +/- 3.5 minutes (P = 0.002) in patients with IDDM. CONCLUSIONS: Changes in blood glucose within the normal postprandial range have a significant impact on gastric emptying in both normal subjects and patients with IDDM.

Increased prevalence of upper gastrointestinal symptoms in long-term type 1 diabetes mellitus.

Using a validated postal questionnaire, we investigated the frequency of 24 gastrointestinal symptoms during the previous 3 months in a cohort of 110 young adult patients (54 males and 56 females, mean age 37.2 +/- 4.7 years) with onset of Type 1 diabetes mellitus at < 16 years of age. They were compared with 210 age- and sex-matched controls (104 males and 106 females). The main difference in the frequency of various symptoms between the two groups was a significant increase among the diabetic patients in upper gastrointestinal symptoms, such as loss of appetite (17.8% vs 3.6%, p < 0.001), early satiety (26.8% vs 6.1%, p < 0.001), nausea (22.7% vs 9.1%, p < 0.01) and vomiting (12.2% vs 3.0%, p < 0.01). No difference was noted in the frequency of symptoms from the lower gastrointestinal tract, apart from a significant increase in the feeling of incomplete defaecation (28.6% vs 17.0%, p < 0.04) in the diabetic patients. Patients with levels of haemoglobin A1c in the highest quartile had significantly more gastrointestinal symptoms than other diabetic patients. Further, the prevalence of symptoms was higher in females than in males. In conclusion, long-term Type 1 diabetes is accompanied by a markedly increased frequency of upper gastrointestinal symptoms, mainly in females and patients with poor metabolic control.

Atropine inhibits the increase in gastric emptying during hypoglycemia in humans.

OBJECTIVE: To study the effect of a cholinergic muscarinic blockade on the gastric emptying rate during insulin-induced hypoglycemia in healthy subjects. RESEARCH DESIGN AND METHODS: In eight healthy subjects, the rate of gastric emptying of an isotope-labeled meal was assessed by a scintigraphic technique during normoglycemia and hypoglycemia with simultaneous infusion of either atropine or saline. Blood glucose concentrations were controlled by an insulin-glucose clamp. RESULTS: The median time for emptying 50% of the liquid phase from the stomach (T50) was 24.9 min (range 13.9-120.0) during normoglycemia compared with 8.1 min (range 3.6-16.5) during hypoglycemia without atropine infusion (P = 0.0005). The T50 for the solid phase was 26.8 min (range 9.7-74.0) and 43.1 min (range 29-57.8), respectively (P = 0.007). During hypoglycemia with atropine infusion, T50 was 40.7 min (range 10.0-120.0) for the liquid phase and 111.4 min (range 38.9-120.0) for the solid phase, not statistically different from normoglycemic examinations. CONCLUSIONS: Cholinergic muscarinic blockade with atropine inhibits the increase in gastric emptying during hypoglycemia. Vagal activity seems to be an important determinant of gastric emptying during hypoglycemia.

Hypoglycemia increases the gastric emptying rate in healthy subjects.

OBJECTIVES: To compare the gastric emptying rate during normoglycemia with that during insulin-induced hypoglycemia in healthy subjects. RESEARCH DESIGN AND METHODS: In eight healthy subjects, the rate of gastric emptying of an isotope-labeled meal was assessed by a scintigraphic technique during normoglycemia and hypoglycemia, both controlled by an insulin-glucose clamp. RESULTS: The mean time taken to empty 50% of the test meal from the stomach (T50) for the solid phase was 43.0 +/- 20.0 min during normoglycemia, compared with 16.3 +/- 6.6 min during hypoglycemia, P < 0.001. The mean T50 for the liquid phase was 38.0 +/- 21.2 and 15.4 +/- 10.6 min, respectively, P < 0.001. CONCLUSIONS: Insulin-induced hypoglycemia increases the gastric emptying rate in healthy subjects.

Hypoglycaemia increases the gastric emptying rate in patients with type 1 diabetes mellitus.

The effect of insulin-induced hypoglycaemia on the gastric emptying rate was studied in eight patients with Type 1 diabetes mellitus of short duration (1-5 years). Gastric emptying was studied using a scintigraphic technique. All patients were studied twice, both during euglycaemia and insulin-induced hypoglycaemia. The blood glucose concentration was adjusted with an insulin-glucose clamp technique. All patients were examined in a standardized way, undergoing the first examination during euglycaemia, with a blood glucose concentration of 4-7 mmol l-1, and the second during hypoglycaemia, with a mean blood glucose concentration of 1.9 +/- 0.3 mmol l-1 at the time of starting the gastric emptying study. During hypoglycaemia both the liquid and the solid gastric emptying rates were significantly increased compared to the rate during euglycaemia. The time to empty 50% of the radioactivity from the stomach for liquid was 48.5 +/- 9.8 min during euglycaemia, compared to 27.6 +/- 20.2 min during hypoglycaemia, p < 0.001. The time to empty 50% of the radioactivity from the stomach for solid food was 48.7 +/- 10.3 min and 23.2 +/- 15.9 min, respectively, p < 0.001. In conclusion, it appears that insulin-induced hypoglycaemia increases the gastric emptying rate in patients with Type 1 diabetes mellitus.

Incidence of symptomatic mild hypoglycaemic events: a prospective study in adult patients with insulin-treated diabetes mellitus using a portable microcomputer-based data-logger.

A new method for recording mild symptomatic hypoglycaemic events was evaluated. A pilot study was conducted using a portable microcomputer-based data-logger which was carried for 10 days by 38 adult patients with insulin-treated diabetes mellitus. The patients recorded symptomatic hypoglycaemic events, meals and sleeping-hours. The recording was prospective and continuous and did not allow any corrections afterwards. No patients had any problems in carrying or handling the data-logger and compliance was good. A total of 76 hypoglycaemic events were recorded in 29 patients. Two patients had hypoglycaemic events that they were unable to manage without help from another person. There was a peak in the incidence of hypoglycaemic events late postprandially, particularly in patients treated with a four-dose insulin regime with fast-acting insulin before meals. A portable microcomputer-based data-logger is a reliable new method for recording symptomatic mild hypoglycaemic events. The incidence of mild hypoglycaemic events was higher than previously reported.