The peroxisome proliferator activated receptorgamma2 (PPARgamma2) Pro12Ala variant: lack of association with type 2 diabetes in obese and non obese Tunisian patients.

OBJECTIVES: Peroxisome proliferator activated receptorgamma2 (PPARgamma2) is a nuclear receptor that regulates adipocyte differentiation, lipid metabolism and probably insulin sensitivity. There have been several reports on the relationship between the PPARgamma2 Pro12Ala genotype and the development of obesity or type 2 diabetes. We designed a case-controlled study to investigate the potential association of the genetic variation of the PPARgamma2 gene with type 2 diabetes in Tunisians. METHODS: We used the polymerase chain reaction and restriction enzyme digestion to characterize the variation of the Pro12Ala polymorphism of the PPARgamma2 gene in 242 unrelated Tunisian patients with type 2 diabetes and 246 healthy control subjects. RESULTS: Analysis of the Pro12Ala polymorphism of the PPARgamma2 gene in patients with type 2 diabetes and in control subjects revealed no significant differences in the PPARgamma2 allele frequencies between diabetic patients and control subjects. However the PPARgamma2 Ala12 allele was found significantly associated with a high level of systolic blood pressure in diabetic patients. Stratification of diabetic patients on obese and non obese subjects showed non significant differences in the PPARgamma2 Ala12 frequency between the two groups. CONCLUSION: These results suggest that the PPARgamma2 gene is unlikely a major gene for type 2 diabetes mellitus or obesity in Tunisian subjects.

Polymorphism of stress protein HSP70-2 gene in Tunisians: susceptibility implications in type 2 diabetes and obesity.

OBJECTIVES: Tumor necrosis factor alpha (TNFalpha) is expressed primarily in adipocytes and elevated levels of this cytokine have been linked to obesity and insulin resistance. Several studies have shown statistical evidence of linkage between obesity and the chromosomal region encompassing the TNFalpha gene, suggesting that TNF alpha and/or a nearby gene is involved in the pathogenesis of obesity. Recently we analyzed the -308 TNFalpha polymorphism and that of HSP70-2 gene in Tunisian patients with obesity and no significant difference in allele frequencies of the -308 TNFalpha polymorphism was found between obese patients and controls. In contrast, polymorphism in HSP70-2 gene was found to be highly associated with obesity. Both TNFalpha and HSP70-2 genes have been mapped within the major histocompatibility complex (MHC). We designated a case-controlled study to investigate a potential association of genetic variation of the TNFalpha and that of the heat shock protein 70-2 (HSP70-2) with type 2 diabetes. METHODS: We used the polymerase chain reaction and restriction enzyme to characterize the variation of the TNFalpha promoter region and that of the HSP70-2 gene in 280 unrelated Tunisian patients with type2 diabetes and 274 healthy control subjects. RESULTS: Analysis of the -308 TNFalpha polymorphism in patients with type 2 diabetes and in control subjects revealed that the heterozygous TNF1/TNF2 genotype was significantly less frequent in the patient group (p=0.003), suggesting that TNF1/TNF2 may be considered as a protective marker against type 2 diabetes (OR=0.58). In contrast, a significant relative risk of type 2 diabetes was found associated with the P2-HSP70-2 homozygous genotype in non obese diabetic subjects (OR=1.97; p=0.0012). CONCLUSION: These results along with those showing high frequency of P2-HSP70-2 genotype in obese Tunisians, suggest that HSP70-2 polymorphism has susceptibility implications in both obesity and diabetes.

Diabetic pregnancy in over 35 years old women.

87 pregnancies in diabetic women older than 35 years at time of conception were studied. 3% were insulin-dependent diabetes mellitus (IDDM), 52% non insulin-dependent diabetes mellitus (NIDDM) and 45% gestational diabetes mellitus (GDM). Mean age was 38 +/- 3 years; BMI was 33.2 +/- 7.0 kg/m2; gestation rate was 5 +/- 3 and number of alive children was 2 +/- 2. Only 3% of pregnancies were planned. Mean time of reference to diabetic care unit was 17 +/- 10 weeks. 95% of the women required human insulin. Mean total daily insulin dose was 0.49 +/- 0.28 UI/kg/d, increasing with gestational age. Mean fasting glycemia was 6.85 +/- 1.93 mmol/l and mean post-prandial glycemia was 8.29 +/- 2.52 mmol/l. Mean time of delivery was 38 +/- 2.1 weeks (less than 37 weeks in 9%). Cesarean section was performed in 44% of 34 cases. Death in utero occurred in 11% of 54 cases, postnatal death in 4%, congenital malformations in 4%, macrosomia in 40%. 9% of infants received intensive neonatal care. No difference was found between NIDDM and GDM about outcome of pregnancy. These results underlined importance of early screening for GDM as most cases seem to be undiagnosed pregravid diabetes mellitus (DM).

[Effect of Ramadan fasting on intragastric pH recorded during 24 hours in healthy subjects]. / Effet du jeûne du ramadan sur le pH intragastrique enregistré sur 24 heures chez le sujet sain.

OBJECTIVES: Lifestyle changes during Ramadan as the meals are taken exclusively in the evening, and nightly sleep is often delayed and shortened. The wake/sleep cycle is also modified. The aim of this study was to evaluate the influence of Ramadan on gastric acidity in healthy volunteers. METHODS: Nine healthy volunteers had 24-hour measurement of the gastric pH; 4 periods were compared: one week prior to Ramadan, day 10 and day 24 during Ramadan, and one month after Ramadan. The pH profiles and the [H+] activity (area under the curve) were measured during 24 hours, the night phase (5PM-8AM) and diurnal phase (8AM-5PM). RESULTS: The diurnal variations of the pH profile were more significant; the median pH was 2.3 prior to Ramadan, 1 at day 10 and day 24 and 1.6 one month after Ramadan. The 24-hours [H+] activity increased by 45% at day 10 of Ramadan compared with its level prior to Ramadan. This increase was mostly diurnal (+122%) and also nightly (+25%). The activity [H+] was steady during Ramadan. One month after Ramadan, the 24-hours [H+] activity was 23% higher than the one noted before Ramadan. CONCLUSIONS: This study shows that the conditions of feeding imposed by Ramadan are associated with an increase of the gastric acidity mainly in diurnal phase. These results do not explain the origin of the healthy volunteer digestive symptoms encountered during Ramadan.