Does holiday hypoglycaemia exist?

BACKGROUND: To determine whether an excessive, prolonged and, above all, unusual physical exertion could be associated with episodes of mild hypoglycaemia in non-insulin-dependent diabetes mellitus (NIDDM) patients treated with glibenclamide. EXPERIMENTAL DESIGN: 11 months of observation with retrospective analysis of patient personal diaries to determine the hypoglycaemic risk. SETTING: Diabetic Unit-Department of Medicine and Aging-Chieti University School of Medicine. PATIENTS: We enrolled 340 NIDDM outpatients adjusted for sex, age, body mass index, alcohol intake and oral treatment regimen with glibenclamide. PATIENTS were tested monthly for circadian blood glucose profiles and glycosylated hemoglobin. Mild hypoglycaemia was defined on the basis of blood glucose values < 2.8 mmol/l associated with mild autonomic symptoms, without requiring external assistance. Each diabetic patient filled personal diary indicating the therapy regimen and the characteristics of eventual hypoglycaemic episodes occurring during the observation period. RESULTS: 21.8% of NIDDM patients experienced one or two episodes of mild hypoglycaemia during the observation period. The analysis of the patients' diaries showed that 60% of the hypoglycaemic episodes was associated with excessive, prolonged and unexpected physical exertions. Within this group, about 70% of the episodes occurred during a holiday ("holiday hypoglycaemia"). After analyzing the socio-demographic and clinical characteristics of the diabetic patients reporting hypoglycaemic events, we found a higher risk for "holiday hypoglycaemia" in patients with a lower educational level, with a sedentary occupation or among the ex-farmers. CONCLUSIONS: As resulted in the present study, unexpected physical exertions may represent a relevant cause of mild hypoglycaemia in diabetic patients receiving oral antidiabetic therapy. However, this hypoglycaemic cause may have been underestimated in the literature. Educational programs conducted by general practitioners or diabetologists could be useful for the patients in reducing the number of mild hypoglycaemic episodes.

Interaction between the G1057D variant of IRS-2 and overweight in the pathogenesis of type 2 diabetes.

The insulin receptor substrate-2 (IRS-2) is a major insulin signalling molecule. IRS-2 inactivation in mice induces a form of diabetes characterized by peripheral insulin resistance and reduced beta cell mass. We tested the hypothesis that a common non-conservative amino acid substitution of IRS-2 (G1057D) might interact with overweight in the pathogenesis of type 2 diabetes. The variant was genotyped in 193 Italian patients with type 2 diabetes and 206 control subjects. In the absence of overweight, the risk of type 2 diabetes decreased according to the dosage of the D1057 allele (odds ratio for GD genotype 0.46 [95% CI 0.25-0.86]; DD genotype 0.18 [0.04-0.68]; P for trend = 0.0012). Conversely, the interaction between overweight and genotype increased the risk of type 2 diabetes according to the dosage of the D1057 allele (odds ratio for GD genotype 2.50 [1.11-5.65]; DD genotype 5.74 [1.11-29. 78]; P for trend = 0.0047). Among controls, fasting C-peptide levels, after adjustment for plasma glucose, were inversely related to the dosage of the D1057 allele (P = 0.020). This finding suggested that carriers of the D1057 allele may have higher insulin sensitivity and supported the protective effect of this allele. Conversely, among overweight patients there was a parallel increase in fasting plasma glucose (P for trend = 0.037) and fasting C-peptide according to the dosage of the D1057 allele, suggesting that higher insulin resistance and relative beta cell failure contributed to the increased risk of type 2 diabetes in overweight carriers of this allele. These data provide evidence for a strong association between type 2 diabetes and the G1057D common genetic variant of IRS-2, which appears to be protective against type 2 diabetes in a codominant fashion. Overweight appears to modify the effect of this polymorphism toward a higher risk of type 2 diabetes. Carriers of this polymorphism may represent an elective target for prevention of type 2 diabetes through preventing or treating excessive weight.

Novel allele of the insulin receptor substrate-1 bearing two non-conservative amino acid substitutions in a patient with noninsulin-dependent diabetes mellitus. Mutations in brief no. 130. Online.

We analyzed by SSCP the complete IRS-1 coding sequence in NIDDM patient #25 D. Unique conformers corresponding to a Ser to Tyr substitution at codon 1043 (S1043Y), and to a Cys to Tyr substitution at codon 1095 (C1095Y) were detected in this patient. The results of sequential digestion with restriction enzymes indicated that the novel sequence variants segregate on the same allele. Relatives of patient #25 D were not available for study, to confirm segregation of the novel allele with NIDDM in the family. Several lines of evidence suggest that the non-conservative amino acid substitutions detected in NIDDM patient #25 D have the potential to affect IRS-1 functions and could play a pathogenic role in this patient. Both S1043Y and C1095Y occur in a highly conserved sequence from human skeletal muscle, human hepatoma, mouse, and rat IRS-1. Protein subsequence analysis revealed that the S1043Y substitution abolishes a consensus sequence for glycogen synthase kinase 3 phosphorylation. Furthermore, S1043Y and C1095Y are not common IRS-1 polymorphisms as they were detected only in 1/136 choromosomes from NIDDM patients (allele frequency in NIDDM patients = 0.0007) and in 0/120 chromosomes from control subjects.

Long-term treatment with fenfluramine in obese subjects.

The effect of fenfluramine, an anorectical drug, given for nine months to a group of 156 obese subjects, on body-weight and adipose mass reduction as well as on glucose tolerance, has been studied. Subjects were divided in four different groups according to various protocols of therapy: the first group took the drug once a day in a single 60 mg dose in the morning; the second group received the drug once a day in a single 40 mg dose in the morning; the third group took the drug divided in three equal daily doses and the last group was treated with diet alone. During the first three months of treatment, fenfluramine 60 mg, given both in a single dose in the morning and divided in three equal daily doses, combined with diet, produces a significant body-weight reduction in comparison with the group of obese subjects treated with diet alone. In the following three months, it was possible to document a further body weight loss in all subjects, whatever the group to which they were assigned. At the end of the sixth month of observation, only slight differences could be demonstrated among the groups as regards the body-weight and adipose mass decrease. In addition the results failed to demonstrate a statistically different weight loss when the drug as administered in a single dose in the morning, compared with the conventional treatment of three times a day. No significant improvement of glucose tolerance was documented. In conclusion, in long-term treatment with fenfluramine, in contrast with short-term studies, no direct effect of this drug on body-weight and adipose mass decrease was demonstrated.

[Chronotherapy of obesity. II. Variations in eating behavior in the obese after fenfluramine treatment in relation to time of administration]. / Cronoterapia dell "obesita'. II. Variazioni del comportamento nell'assunzione del cibo in obesi sottoposti a trattamento con fenfluramina in relazione all'ora di somministrazione.

The administration of Fenfluramine (F.) in a single dose in the morning provokes a different effect on eating behavior (E.B.) in comparison with the administration of the same dose three times/day. It is observed a shorter duration of eating (p less than 001); a decrease of total kcalories ingested during the day, and hunger feeling. These results are reviewed on the basis of present knowledge on drug-kinetic and on previous work in our laboratory which documented higher decrease of body weight and adipose mass when the F. was administered in a single dose in the morning than in the afternoon or three times a day.

[The TRH test in latent thyroid pathology]. / Il TRH-test nella patologia tiroidea latente.

TRH-test is an usefull tool for diagnostic purpose in thyroid disease. We challenged with TRH 4 groups of patients (1 degrees non toxic diffuse goitre, 2 degrees nodular goitre (Plummer's disease), 3 degrees euthyroid ophthalmic Graves' disease, 4 degrees hemithyroidectomy) with different thyroid affections who showed no symptoms and presented normal values of total thyroid hormones, in comparison with a control group. These groups displayed normal and pathological (blunted or absent and exaggerated) responses of TSH to TRH. Therefore TRH-test ra presents a good mean to recognize subclinical forms both hyperthyroidism and hypothyroidism.

[Effects of a "single-meal" low calorie diet on the circadian variation of serum cortisol, insulin and somatotropin and urinary excretion of catecholamines]. / Effetti di una dieta ipocalorica "monopasto" sulla variazione circadiana di cortisolemia, insulinemia, somatotropinemia ed escrezione urinaria delle ca tecolamine.

Four obese patients were given a single-meal diet for two periods of three days each. Blood samples were drawn every four hours for serum determinations of growthormone, cortisol and insulin. At same times urinary samples for urinary cathecholamines determination were collected. Cortisolemia showed a firm circadian rhythm in both regimens: there was a marked over-lap of the two confidences ellipsis so we could conclude for the independence of cortisol rhythm whith both regimes, but there occurred a significant difference in the acrofases between the two regimens. This could mean that meal-timing can play a major role in syncronizing catecholamines urinary excretion as far as subjects in supine position are concerned. No circadian rhythm was detected either in serum insulin or in HGH values.

[Modifications of the water balance and urinary excretion of sodium and potassium in obese subjects on a "single-meal" low-calorie diet]. / Modificazioni del bilancio idrico e della escrezione urinaria del sudio e del potassio in soggetti obesi sottoposti a dieta ipocalorica "monopasto" Rilievi cronobiologici.

Four obese patients were given a single-meal diet (684 kcal.) for two periods of three days each. Water-loss, according to Peter-Passmore formula, and urinary sodium and potassium excretion were measured at 4-hours intervals. A water-loss greater in the first than in the second and in the third day in both periods and a strong linear correlation between water-loss and sodium urinary excretion were found. Furthermore a circadian rhythm either is sodium or in potassium urinary excretion not modifiable by meal timing with both regiment was detected.

[Variations in carbohydrate, lipid and protein oxidation evaluated by indirect calorimetry in obese subjects on a "single-meal" low-calorie diet]. / Variazioni del'ossidazione glucidica lipidica E protidica valutate mediante calorimetria indiretta in soggetti obesi sottoposti a dieta "monopasto".

Four obese patients were given a single-meal diet (Kcal, 684) for two periods of three days each. CO2 production and 02 consumption were measured every four hours for 30'. At the same times urine samples were collected for nitrogen evaluations. By Consolatio's formulas the amount of carbohydrates, lipids and proteins oxidated in the three days of both periods was calculated. No changes in carbohydrate and lipid oxidation rates were found during the three days with meal at h.10, while a progressive increase in lipid oxidation and a progressive decrease in carbohydrates oxidation could be observed with meal at h. 18. No change with both regimes could be observed in protein oxidation. Furthermore a circadian rhythm of lipid and carbohydrate oxidation with both regimens was observed, while protein oxidation showed a circadian rhythm only with meal at h.10.

[Preliminary results of an epidemiological survey for diabetes]. / Risultati preliminari di una indagine epidemiologica per il diabete

Mass screening for diabetes in a factory employing 464 subjects by means of a 75 g oral glucose tolerance test and measurement of blood sugar with Dextrosix reagent strips read on a reflectance meter is reported. Values of 120 mg% or over were noted in 10.34% and values in the range 110 to 120 mg% in 7.76%.