Prevalence of elevated liver enzymes in Type 2 diabetes mellitus and its association with the metabolic syndrome.

The occurrence of liver disease and raised liver enzymes is common in Type 2 diabetes, and may be multifactorial in origin. Very few studies are available on the exact prevalence of the phenomenon, however. We carried out an observational point-prevalence study of elevated liver enzymes in eight hospital-based Italian diabetes units. Data of 9621 consecutive Type 2 diabetes patients (males, 52.4%; median age, 65 yr) were analyzed, and alanine and aspartate aminotransferase (ALT, AST) and gamma-glutamyltransferase (GGT) levels were related to body mass index (BMI), metabolic control and the presence of the metabolic syndrome. ALT, AST, and GGT levels exceeding the upper limit of normal were present in 16.0%, 8.8%, 23.1%, respectively, the prevalence being higher in males, increasing with obesity class and poor metabolic control, and decreasing with age. Elevated enzymes were systematically associated with most parameters of the metabolic syndrome. After correction for age, gender, BMI, and differences across centers, elevated triglyceride levels/fibrate treatment [odds ratio (OR), 1.57; 95% confidence interval (CI), 1.34- 1.84] and an enlarged waist circumference (OR, 1.47; 95% CI, 1.17-1.85) were the only parameters independently associated with high ALT. In a separate analysis, the presence of metabolic syndrome (Adult Treatment Panel III criteria) was highly predictive of raised liver enzymes. After exclusion of hepatitis B and C positive cases, tested in 2 centers, the prevalence of raised enzymes decreased by approximately 4%, but the association with the metabolic syndrome did not change significantly. In conclusion, the high prevalence of elevated liver enzymes in Type 2 diabetes is in keeping with the well-demonstrated risk of progressive liver disease. A large amount of diabetes patients may require a thorough clinical, laboratory and histological investigation.

Outcome of pregnancy in type 1 diabetic patients treated with insulin lispro or regular insulin: an Italian experience.

Some studies have shown that fetal outcome observed in patients using insulin lispro is much the same as in pregnant women using regular insulin. This study aims to analyze the Italian data emerging from a multinational, multicenter, retrospective study on mothers with type 1 diabetes mellitus before pregnancy, comparing those treated with insulin lispro for at least 3 months before and 3 months after conception with those treated with regular insulin. The data collected on pregnant women with diabetes attending 15 Italian centers from 1998 to 2001 included: HbA1c at conception and during the first and third trimesters, frequency of severe hypoglycemic episodes, spontaneous abortions, mode and time of delivery, fetal malformations and mortality. Seventy-two diabetic pregnancies treated with lispro and 298 treated with regular insulin were analyzed, revealing a trend towards fewer hypoglycemic episodes in the former, who also had a significantly greater reduction in HbA1c during the first trimester. The rate of congenital malformations was similar in the offspring of the two groups of women treated with insulin lispro or regular insulin. These findings suggest that insulin lispro could be useful for the treatment of hyperglycemia in type 1 diabetic pregnant women.

Expression of PACAP and its type-I receptor isoforms in the rat ovary.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a member of the secretin/glucagon/vasoactive intestinal peptide (VIP)/growth hormone releasing hormone (GHRH) family of neuropeptides, several of which stimulate steroidogenesis in ovarian granulosa cells. PACAP receptors are of two major subtypes; the type I receptor (PACAP-I-R) has much higher affinity for PACAP than VIP, and the type II receptor (PACAP-II-R) has similar affinity for both peptides. In the rat ovary, expression of the PACAP gene was demonstrated by amplification of ovarian RNA by the reverse transcription/polymerase chain reaction (RT-PCR). In addition, hybridization of Northern blots of rat ovarian poly(A)+ RNA with a 706-nt rat hypothalamic PACAP-I-R cDNA probe revealed the presence of a 7.0 kb PACAP receptor transcript, similar to that detected in brain and hypothalamus. RT-PCR using specific primers for the PACAP-I-R gene yielded products of the expected size with RNA obtained from ovarian tissue, brain, and hypothalamus. The authenticity of the PCR products was confirmed by Southern blotting and nested PCR, which revealed at least three splice variants of the PACAP-I-R in the rat ovary. These findings demonstrate that both PACAP and PACAP-I-R isoforms are expressed in the rat ovary, where they could exert autocrine or paracrine actions on granulosa cell function.