| BackgroundDue to the rapid increase of the incidence and prevalence of obesity and diabetes, pre-diabetes prevalence rate in obese patients is higher. The risk of diabetes in pre-diabetes increased from3to10times,the risk is higher in particular race. Epidemiological studies have shown that the risk of complications began in the early stage of diabetes. So early diagnosis and treatment of pre-diabetes will reduce or delay the progress of diabetes mellitus, cardiovascular disease and microvascular disease. Along with the in-depth study of the pathogenesis, there appears a series of anti-diabetic drugs acting on the new targets, sustainable controlling blood sugar, effectively preventing the conditions from deteriorating. The most noticeable samples are Glucagon-Like Peptide-1(GLP-1) analogue and Dipepitidyl Peptidase-4(DPP-4) inhibitors. At the beginning of the20th century, it was found that oral glucose significantly stimulate more secretion of insulin than intravenous, the phenomenon of " incretin effect ". GLP-1stimulate the biological synthesis and secretion of insulin, restrain glucagon release, delay gastric emptying and have a protective effect on beta cell. But the DPP-4in the body can quickly and specificity crack GLP-1peptides N-terminal2nd proline or alanine, which result in GLP-1’s inactivation. The Inhibitors of DPP-4can increase the half-life of GLP-1and extend its beneficial effect, which lead DPP-4inhibitor become a promising Type2diabetes treatment.ObjetctiveBy using DPP-4inhibitors Saxagliptin and lifestyle intervention on newly diagnosed pre-diabetes obesity people, the project mean to evaluate the DPP-4inhibitors’ effect of reversing pre-diabetes to normal glucose tolerance, and observe the influences on obesity related metabolic abnormalities, thus to explore new intervening measures of the obese pre-diabetes. MethodsThis is a prospective, randomized controlled clinical study, all the research object are collected from endocrinology outpatient in the Provincial Hospital Affiliated to Shandong University. The aim is to evaluate the Saxagliptin monotherapy efficacy on newly diagnosed obese pre-diabetes. A total of27patients was collected, including14male,13female, they were randomly divided into:the lifestyle intervention with Saxagliptin (5mg/day) group, the lifestyle intervention group, the lifestyle intervention with metformin (500mg/three times a day)group, the lifestyle intervention with Saxagliptin (2.5mg/day). Interventions lasts on a total of3months. We carry out a medical examination respectively on the newly diagnosed,1month after intervention and3months after intervention (including blood pressure, weight, height, waist circumference, hip circumference, etc.), Body fat composition determination, laboratory examination(including blood routine, fasting and postprandial, fasting insulin, blood fat, liver function, myocardial enzyme, etc.); Detection of HbAlC is carried out on the newly diagnosed and3months after intervention;75g oral glucose tolerance test (OGTT) and insulin release test (OGIRT) are carried out on the newly diagnosed after interventionto evaluate the islet cell function and insulin resistance.Results1. After3months intervention we can see Saxagliptin group has a better postprandial blood glucose control compared with the simple lifestyle intervention group (P<0.01) and metformin group (P<0.05);2. After3months intervention we can see the insulin resistance index of Saxagliptin group is lower than the simple lifestyle intervention group group (P<0.01);3. After3months intervention we can see the beta cell of islet function index of the Saxagliptin group is higher than the simple lifestyle intervention group group (P<0.05);4. After3months intervention we can see the body fat of the Saxagliptin group is lower than the simple lifestyle intervention group group, but there was no statistically significant difference (P>0.05),the body fat of the metformin group was lower than other group (P<0.05).Conclusions3months of Saxagliptin monotherapy can bring obese pre-diabetes better blood sugar control, particularly on the postprandial blood glucose control; Saxagliptin monotherapy can bring obese pre-diabetes effectively improvement of insulin resistance and islet beta cell function; Saxagliptin monotherapy is of little influence on the distribution of body fat, while the metformin can reduce body fat. The lipodystrophies are a rare syndrome characterized by variable loss of adipose tissue, which always in the company of metabolic complications, such as insulin resistance, impaired glucose tolerance, diabetes, fatty liver, hypertriglyceridemia, high basal metabolic rate and so on. The lipodystrophies can be classified into two major types according to genetic principles:familial and acquired. On the basis of the position and extent of fat loss it can also be devided into two subtypes:generaliazed and partial. Acquired Generalized Lipodystrophy(AGL) has multiple pathogenesis, which characterized by a generalized loss of subcutaneous adipose tissue Spread over the face, neck, limbs and trunk and a paucity of subcutaneous fat in the palms and soles, however some patients have intraabdominal and bone marrow fat spared, it usually occurred during childhood or later, and AGL patients are highly likely to develop severe hyperinsulinemia, insulin resistance, diabetes, hypertriglyceridemia, fatty liver, acanthosis nigricans,etc. It can be divided into three types, type1patients have panniculitis before lipodystrophy, which is start with local fat atrophy caused by subcutaneous inflammatory nodules and it can extended to the whole body later; Patients with type2have autoimmune disease, such as juvenile dermatomyositis besides lipodystrophy. Type3is idiopathic AGL, accounting for50%. We found a16years old female patient complained of "dry mouth, polydipsia, polyuria and weight loss for3months". The patient is thin and also exist the acanthosis nigricans in the neck and armpits, high level of serum triglyceride and low serum HDL cholesterol concentrations, insulin resistance, diabetes, fatty liver, damaged liver function. The bone mineral density was measured by dual-energy-X-ray, which may suggest the diagnosis of severe osteoporosis. The clinical features of the patient cannot be ruled out of familiar partial lipodystrophy (FPLD), so we carried on the LMNA gene detection, results show that the target gene exon coding region has no pathogenic mutations, this greatly reduces the likelihood of the patient suffering from FPLD. Her diagnosis is acquired generalized lipodystrophy. The treatment is focus on hepatoprotective, lipid-modulating, blood sugar controlling treatment. Liver function, blood lipid and glucose have effective improvement after3months of treatment, while the lipodystrophy has no obvious improvement. So far there is no report of patients who have lipodystrophy suffering from osteoporosis in the meantime.Considering the patient have no symptoms related to osteoporosis, we suggested that patient to have adequate illumination, moderate calcium and vitamin D intake, periodic detection of bone mineral density. A thorough physical examination and detailed laboratory tests of "lean" diabetics with these metabolic complications above should be inspected screening the fat loss, to reduce the misdiagnosis. |
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