Safety of metformin in the treatment of elderly type 2 diabetes mellitus / 中华内科杂志

Objective To evaluate the safety of mefformin in the treatment of elderly type 2 diabetes mellitus(T2DM). Methods Two hundred and forty-three cases of elderly T2DM hospitalized from Jan.1996 to Dec. 2006 were reviewed; the changes of fasting blood glucose(FBG), postprandial blood glucose (PBG), glycosylated hemoglobin (HbA1c), liver and renal function and blood lactic acid were evaluate before and after treatment. Results The mean time of treatment with mefformin was (6.6±3.9) years (3 months-21 years)in these 243 cases. The levels of FBG, PBG and HbAlc significantly reduced after treatment with mefformin only in 43 cases (17.7%), mefformin combined with other oral hypoglycemic drugs in 124 cases (51.0%) and mefformin combined with insulin in 76 cases (31.3%). There was only 18.1% of the cases with normal range ( > 80 ml/min) of creatinine clearance rate (Ccr), and 25.8% of the cases with Ccr≤50 ml/min. The liver and renal function as well as the blood lactic acid had no significant change after treatment no matter in total cases or in different groups separated by Ccr.Conclusions Mefformin is safety in the treatment of elderly T2DM patients. Ageing is not the contraindication of mefformin. To the patients with high risk, we should monitoring the level of blood lactic acid.

Genetic variations at urotensin II and urotensin II receptor genes and risk of type 2 diabetes mellitus in Japanese.

Urotensin II is among the most potent vasoactive hormones known and the urotensin II (UTS2) gene is localized to 1p36-p32, one of the regions reported to show possible linkage with type 2 diabetes in Japanese. When we surveyed genetic polymorphisms in the UTS2 and urotensin II receptor (GPR14) gene, we identified two SNPs with amino acid substitutions (designated T21M and S89N and an SNP in the promotor region (-605G>A) of the UTS2 gene, and two SNPs in the non-coding region of the GPR14 gene. We then studied these three SNPs in the UTS2 gene and two SNPs in the GPR14 gene in 152 Japanese subjects with type 2 diabetes mellitus and two control Japanese populations. The allele frequency of 89N was significantly higher in type 2 diabetic patients than in both elderly normal subjects (P = 0.0018) and subjects with normal glucose tolerance (P = 0.0011), whereas the allele frequency of T21M and -605G>A in the UTS2 gene and those of two SNPs in the GPR14 gene were essentially identical in these three groups. Furthermore, in the subjects with normal glucose tolerance, 89N was associated with significantly higher insulin levels on oral glucose tolerance test, suggesting reduced insulin sensitivity in subjects with 89N. These results strongly suggest that subjects with S89N in the UTS2 gene are more insulin-resistant and thus more susceptible to type 2 diabetes mellitus development.

THE CHANGES IN PLASMA ACTH, SERUM CORTISOL AND UFC IN PATIENTS WITH ADRENAL INSUFFICIENCY / 解放军医学杂志

To evaluate the significance of plasma ACTH, serum cortisol and UFC levels as well as ACTH stimulation test, aminoglutethimide test and insulin induced hypoglycemia test in patients with adrenal insufficiency. Sixteen patients with primary insufficiency (Addison`s disease) and 75 cases with secondary insufficiency (hypopituitarism) diagnosed from 1985 to 1999 were reviewed. It was found that high levels of ACTH were detected in all patients with primary insufficiency, and in most of them the levels of cortisol and UFC were low. No response of cortisol and UFC were observed after ACTH stimulation in the patients with primary insufficiency, but normal or delayed action was observed in the patients with secondary adrenal insufficiency. In most of secondary adrenal insufficiency the ACTH levels were in normal range but the cortisol and UFC levels were low; the elevated action of ACTH by insulin induced hypoglycemia test or aminoglutethimide test did not appear in the patients with secondary adrenal insufficiency. The results suggested that the low levels of cortisol and UFC were a common feature in the most of patients both with primary or secondary adrenal insufficiency. The ACTH level was the key indicator to distinguish the primary adrenal insufficiency from secondary adrenal insufficiency, as the ACTH levels were remarkably elevated in primary patients but were normal or decreased in secondary insufficiency patients. The ACTH stimulation test was useful in the diagnosis of the primary or secondary adrenal insufficiency. The insulin induced hypoglycemia test or aminoglutethimide test was valuable in the diagnosis of the secondary adrenal insufficiency.

THE CHARACTERISTICS OF PLASMA ACTH, SERUM CORTISOL AND UFC IN 136 PATIENTS WITH CUSHING SYNDROME / 解放军医学杂志

To evaluate the significance of plasma ACTH (pACTH), serum cortisol (SC) and urinary free cortisol UFC as well as low or high dose dexamethasone suppression test in Cushing syndrome, the levels of hormones were evaluated in 136 cases of Cushing syndrome. It was found that the levels of SC and UFC were elevated in almost all the 121 patients with Cushing syndrome. The mean levels of pACTH were higher in 86 patients with Cushing disease and lower in 36 cases with adrenocortical tumor or ACTH independent nodular adrenocortical hyperplasia (AINAH) than those in normal subjects. The ACTH levels might be in normal range in many patients with Cushing syndrome, but they were higher in patients with Cushing disease and lower in the patients with adrenocortical tumor or AINAH than those of the high limit at ACTH0am in normal subjects. It was a common feature that the diurnal rhythm of hormone secretion disappeared and the hormone levels were not suppressed by low dose dexamethasone suppression test in the patients with Cushing syndrome. In more than 90% of the patients with adrenocortical tumor or AINAH the levels of SC and UFC were not suppressed by high dose dexamethasone. In 12 of clinically cured patients with Cushing disease the levels of pACTH8am, SC8am and UFC were normal or even low. The pACTH levels were low in two patients with iatrogenic Cushing syndrome. The results suggested that examinations of SC, UFC and low dose dexamethasone suppression test were very important in the diagnosis of Cushing syndrome. The pACTH level was a key parameter to distinguish Cushing disease from adrenocortical tumor or AINAH.