Mitochondrial mutation in Egyptian patients with type 2 diabetes mellitus

Mitochondrial gene mutation plays a role in the development of diabetes mellitus. An A to G substitution at base pair 3243 in the mitochondrial tRNAleu[UUR] gene [mt3243] is commonly associated with maternally inherited diabetes and deafness and other diseases. The aim of this study is to detect A to G substitution at base pair 3243 in mitochondrial RNAleu[UUR] in the plasma of patients with type 2 diabetes mellitus, and to evaluate insulin sensitivity in all cases. This study, included 41 patients [Group I, 31 cases with type 2 diabetes mellitus and maternal history of diabetes mellitus-and Group II, 10 cases with type 2 diabetes mellitus, bilateral SNHL, maternal history of diabetes mellitus with or without SNHL. Other10 healthy control group was included. Patients and controls were subjected to full medical history and clinical examination. Serum measurements for liver and kidney function tests, fasting and postprandial blood glucose as well as C-peptide levels, in addition to lipid profile were collected. Audiological evaluation for all patients with SNHL was also done. Genetic investigation, for mDNA analysis, done by polymerase chain reaction restriction fragment length polymorphism [PCR-RFLP], to determine the mutation in the mitochondrial gene at position 3243. Results of the study showed that glycemic indices [FPG, 2hPPG and HbA1c], liver enzymes and blood urea were significantly higher among patient group compared to control group [P<0.05]. There was no significant difference for values of creatinine and uric acid between cases and controls. Lipid profile was significantly higher among patient group compared to controls [P<0.05], except for HDL-C which was higher in controls however, it did not reach statistical significance. C-peptide values were not significantly different between studied groups. Age at onset of diabetes was relatively earlier in group II than group I. mDNA was present in all plasma samples of patients and controls. mDNA 3243 mutation was detected in the plasma of three patients with diabetes and SNHL with a rate of 7.3% of all diabetic patients and 30% of diabetic patients associated with deafness. The presence of mDNA mutation allowed 294 bp product to be cleaved into 180 and 114 bp fragments and were seen as two bands. The A 3243 G mutation is present in Egyptian population and is considered as a cause of maternally inherited diabetes and deafness at a rate of 7.3% of all diabetic subjects and a rate of 30% of diabetics associated with deafness. mDNA mutation is present and detectable in plasma. Maternally inherited diabetes and deafness differs pathophysiologically from the more common forms of type 2 diabetes in that, insulin resistance does not seem to be a major factor

Body fat distribution, serum leptin, and insulin resistance in obese subjects with obstructive sleep Apnoea

Obstructive sleep apnoea [OSA] is strongly associated with obesity and is characterized by endocrine and metabolic changes. The aim of the present study is to clarify whether there is interrelationship between body fat, serum leptin, glucose-insulin metabolism and OSA

Subjects and measurements: We studied 23 obese subjects with OSA [13 males,and 10 females; age mean 36 +/- 4.4 years; BMI: 31.7 +/- 3.6 kg/m2; WHR: 1.2 +/- .25 in males and 0.81+.5 in females ;Apnoea Index "AI"[ 9.2 +/- 6.1] event/hour of sleep by means of overnight polysomnography; fasting glucose[109.8 +/- 21.4 mg/dL] ; fasting insulin[18.6 +/- 7.1 uU/L ]; IR[6.7 +/- 2.8]; fasting leptin[577.69 +/- 201.6 ng/ml]. Results were compared with those of 10 healthy normal weight subjects[6 males,4 females; age mean 36.8 +/- 4.4 years; BMI: 25 +/- 0.24 kg/m2; WHR: 0.86 +/- 0.01; AI: 2.1 +/- 1.1 event/hour; fasting glucose[71.7 +/- 2.8 mg /dL ]; fasting insulin[15.3 +/- . 48 uU/L ]; IR[4.6 +/- . 17]; fasting leptin [42.4 +/- 11.5 ng/ml]

Results: Anthropometric measurements of OSA subjects were highly significantly greater than controls; body weight [P<0.003]; BMI [P<0.00]; waist [P<0.000]; and WHR [P<0.000]. Fasting glucose levels; fasting plasma insulin; IR and leptin levels were significantly higher in OSA subjects than controls [P<0.000, 0.03, 0.002; and 0.000] respectively. Overnight polysomnography revealed significant difference between OSA subjects and controls as regards AI [P<0.001]. The major dependent outcome variable was the apnoea index [AI], "the average number of apnoeas per hour of sleep determined by overnight polysomnography". OSA was defined as AI >/= 5. Highly significant correlation between AI and WHR [P<0.00]; Fasting insulin [P<0.04]; IR [P<001] and Leptin [P<0.000] were detected. Also leptin concentrations correlated with fasting insulin [P<0.02]; IR [P<0.00] and WHR [P<0.000] besides the AI

In Conclusion: There is strong bidirectional, feed-forward pernicious correlation detected between OSA in one side and each of visceral obesity, leptin, and IR; also between leptin, obesity, and IR. This association may contribute to the pathological manifestations and somatic sequale of this condition. Leptin could have major role linking OSA with various metabolic abnormalities detected in obese subjects. High circulating leptin found in this study, suggests that both obesity and OSA may be caused by a leptin resistant state. Among obese subjects, it is visceral fat [WHR], rather than generalized obesity [BMI] that predisposes to OSA

Serum and follicular insulin growth factor [I G F -I] and insulin growth factor binding protein - I [I G F B P -I] In polycstic ovary syndrome

The present study comprised a total of 75 young women [45 polycystic ovary syndrome [PCOS] patients and 30 age and weight matched controls]. On the basis of their body mass index [BMI], the patients and controls were further subdivided into obese [BMI 27 kg/m2] and lean [BMI 25 kg/m2] groups. All participants in the study were subjected to medical as well as reproductive history. A clinical and gynecological examination including pelvic ultrasonography was done. BMI and WHR were also calculated. Hirsutism was examined and graded. Fasting plasma glucose, serum LH, FSH, testosterone, SHBG, insulin, IGF-1 and IGFBP-1 were measured. Fasting glucose/insulin ratio as an indicator of insulin resistance and free androgen index [FAI] as index of hyperandrogenemia were calculated. Moreover, follicular fluid samples were collected from 15 PCOS and 5 control subjects for the assessment of their IGF-1 and IGFBP-1 levels

Triple H syndrome: a novel auto-immune endocrinaopathy characterized by dysfunction of the hippocampas, hair follicle and hypothalamic pituitary - adrenal axis a replication study

In this study, we described two, unrelated adult, female and male patients. They developed sever fatigue, weakness, anxiety postural hypotension and hypoglycemia. Progressive alopecia areata with impairment of antrograde memory were also present. Marked hypocortisolemia, Anti bodies to some endocrinal cells. Associated with radiological abnormalities in the hippocampus were detected. The similarity between these two cases and the uncommon nature of the component abnormalities suggest the involvement of a molecular target for autoimmunity shared among hippocampus, hair follicle and the hypothalamus and/or corticotrophin, it is the cause of its name "Triple H. Syndrome". A German female 41 years old presented to the endocrine department of AI- Aahraa university Hospital in September 2002 with total loss of body hair. In year 2000 the patient noticed progressive constipation, loss of appitite and sleeping tendency. This was associated with loss of memory specially for recent events. Laboratory investigation in the form of free T[3], free T[4], TSH and thyroid AB were done [Table 1], and the patient was diagnosed as having hypothyroidism. She received medical treatment in the form of EI-Troxin 75 Mic. gm/d. and the condition gradually improved. After 7 months of treatment the patient became pregnant, after delivery she started to lose scalp hair gradually, followed tow months later by loss of eye brows, axially and pubic hair. Subsequently she complained of fatigue, memory loss especially for recent events along with symptoms of hypertension and repeated hypoglycemic attacks