Volume 04 · Issue 12 · 2012

Type 2 diabetes mellitus (T2DM) is an outbreak trend worldwide, and the high mortality and disability rate caused by diabetic microvascular and macrovascular complications seriously threaten the physical and mental health of patients^[1]。 Therefore, early screening of diabetes and doing a good job in primary and secondary prevention of diabetes can minimize the occurrence of diabetes-related adverse events and reduce the social burden. At present, in addition to traditional methods, some new methods have emerged in diabetes screening, which provides a brand-new perspective for diabetes screening strategies. This article will briefly comb this.

Type 2 diabetes is a major medical problem that seriously threatens human health. Studies have shown that the probability of developing diabetes in high-risk groups far exceeds that of the general population. When individuals have more diabetes risk factors, the greater the possibility of developing diabetes. However, because the onset of diabetes is somewhat hidden, about 30% of diabetes patients in the United States are missed, and about 25% of newly diagnosed diabetics already have retinopathy or microalbuminuria, which means that patients have been "ignored" for at least 7 years between onset and diagnosis^[1]。 The above situation is more serious in China. The results of the National Diabetes Prevalence Survey from 2007 to 2008 show that about 61.3% of male patients and 59.8% of female patients were passively detected with diabetes through census^[2]。

To enhance the understanding of fibrocalculous pancreatic diabetes (FCPD) by reviewing its clinical features and auxiliary examination results.

Three patients in our hospital were reported in detail. Combined with the clinical data of 50 cases of FCPD had been reported in our country, the sex ratio of patients, age of onset, clinical features, laboratory examination, imaging characteristics and treatment were discussed through retrospective analysis.

In total 53 cases, there were 37 male and 16 famale, the diagnose age was 27-60 years old. These patients were mainly distributed in Sichuan (18 cases), Guangxi (18 cases), and Guangdong (12 cases) province. Some scattered in Hainan (1 case), Guizhou (1 case), Hunan (1 case), Zhejiang (1 case) and Inner Mongolia (1 case). Edible cassava was in 11 cases, and drinking history in 4 cases. One patient was misdiagnosed as type 1 diabetes mellitus(T1DM) for 5 years, and the other 10 patients were diagnosed as type 2 diabetes mellitus(T2DM) for 2-6 years respectively. 33 cases had abdominal pain, 19 patients had steatorrhea. The calculus and fibrosis were confirmed by X-ray (11 case), B ultrasound (30 cases), computed tomography (35 cases), magnatic resonance imaging(MRI) and surgical pathology(1 case). Most of the patients (n=52) had low body weight. Admission random blood glucose levels were 14.0-30.8 mmol/L, plasm insulin and C-peptide were significantly decreased, but only 2 cases had ketosis. 51 cases were treated with insulin, only 2 cases were treated with sulfonylurea oral glucose-lower drugs to control blood sugar.

(1) The classic clinical symptoms of FCPD are abdominal pain, steatorrhea and diabetes but almost atypical. (2)Some findings, including low weight, high blood sugar, poor pancreas islet function and no ketosis, are helpful for making an early and accurate diagnosis. Calculus and fibrosis of pancreas through X-ray, B ultrasound, CT or MRI are useful for the final diagnosis.

To evaluate the impact of continuous positive airway pressure on insulin resistance in obstructive sleep apnea hypopnea syndrome(OSAHS) in Chinese by meta-analysis.

The clinical trials involving continuous positive airway pressure on glucose metabolism in OSAHS in Chinese were searched and identified from PubMed, China Academic Journals full-text database, Chinese Biomedical Literature Database, Wanfang Resource Database, Chongqing VIP and Chinese Journal full-text database. According to inclusion and exclusion criteria and to evaluate the quality of choice experiment, and then extract the valid data.The Stata 11.0 software was used to carry out meta-analysis.

The data part of the results should be added to the 95% confidence interval and 13 articles were ultimately included. Meta analysis showed fasting blood glucose (FBG) was significantly decreased in patients with OSAHS and OSAHS patients with diabetes mellitus after CPAP therapy (WMD=0.473, 95%CI(0.157, 0.790), P=0.003; WMD=1.358, 95%CI(0.921, 1.794), P=0). CPAP had no obvious effect on fasting insulin (FINS) (WMD=0.624, 95%CI(-0.512, 1.759), P=0.282; WMD=0.275, 95%CI(-0.416, 0.965), P=0.435). Whereas it could significantly reduce insulin resistance index (HOMA-IR) in two groups (WMD=0.483, 95%CI(0.119, 0.846), P=0.009; WMD=0.726, 95%CI(0.023, 1.430), P<0.05). In addition, CPAP affected HbA1c in diabetic patients with OSAHS, the difference was statistically significant (WMD=1.03, 95%CI(0.71, 1.34), P<0.05). The funnel plots of FBG, FINS, HOMA-IR, and HbA1c were basically rendered under the wide and narrow symmetrical graphics before and after CPAP treatment, according to Egger’s examination, there had obvious publication bias in HOMA-IR in OSAHS group, the other indexes did not exist significant publication bias.

CPAP can improve insulin resistance in patients with OSAHS whether or not with diabetes. However, due to the quality and the limitations of the studies, more high-quality, large-scale randomized controlled clinical trials are required to be verified.

To explore the value of dual energy X-ray(DEXA) in detection of body fat distribution of type 2 diabetic patients and to analyze the relationships of body fat distribution with insulin resistance and lower extremity vascular disease.

Total of 123 patients with type-2 diabetic mellitus treated in Shanxi People's Hospital from December 2010 to May 2011 were enrolled in this study as investigation group. Local trunk fat content(Trunk%) was measured by using DEXA. One-hundred and twelve healthy subjects receiving health examination in the hospital were enrolled as controls. The waist circumference, height, weight, blood pressure were measured in the two groups. Fasting insulin (FINS), fasting plasma glucose (FPG), total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and glycated hemoglobin A1c(HbA1c) were detected by enzyme-linked immunosorbent assay (ELISA) and automatic biochemical analyzer. Based on the state of diabetes and obesity, the subjects were divided into 4 groups: diabetic and obese group (DMOB group,n=78, 41 males and 37 females), non-obese diabetic group (DMNOB group, n=45, 23 males and 22 females), the obese control group (OB group, n=69, 35 males and 34 females) and non-obese control group (NOB group, n=43, 21 males and 22 females). Measurement data was compared with two-tailed independent-samples t test, and multiple liner regression were used to evaluate the effects of waistline, body mass index(BMI) and trunk% on homeostasis model assessment of insulin resistance (HOMA-IR).

The trunk% of the DMOB, DMNOB, OB and NOB group were 38%±4%, 24%±6%, 38%±5%, 26%±6%, respectively(F=28.704, P<0.05). The level of HOMA-IR in DMOB group was significantly higher than those in DMNOB, OB and NOB group (2.1±1.0, 1.6±0.8, 1.6±0.4 and 1.3±0.4, respectively;F=1.518, P=0.000); the levels of systolic blood pressure(SBP), diastolic blood pressure(DBP), TC, TG in DMOB group were significantly higher than those in DMNOB group (t=2.173-3.058; all P<0.05). And the DBP, HbA1c, TC, TG and LDL-C level in DMNOB group were significantly higher than those in OB and NOB group (F=0.569-47.704, all P<0.05). The multiple liner regression analysis suggested that BMI (OR=1.749, P<0.05) and trunk% (OR=1.987, P<0.05) were influential factors of HOMA-IR. The Spearman analysis showed that trunk%, waist circumference, BMI, SBP, TG, LDL-C, HbA1c, FPG, FINS and HOMA-IR were positively correlated with lower extremity vascular disease in type 2 diabetic patients (r=0.232-0.470, all P<0.05).

Trunk% measured by DEXA can be used to evaluate abdominal obesity, may influence insulin resistance in a certain extent and is related to the degree of lower extremity vascular diseases in type 2 diabetic patients.

To explore the association of glycated hemoglobin A1c(HbA1c) in non-diabetes with the early stage of arteriosclerosis, and evaluate the modification effects of age, blood pressure, lipids et al in non-diabetes Chinese adults.

We performed a community-based health examination survey for 5514 individuals (19-90 yrs old) who were randomly selected from residents living in the urban area of Xuzhou city. In total 5098 non-diabetes individuals were included in the final analyses, physical measurements, biomarkers and carotid-to-femoral pulse wave velocity (c-fPWV) were detected. Data management and statistical analysis were conducted using SPSS 15.0 statistical software, Chi-square test were used to calculate the count data, comparisons between groups were assessed by one-way analysis of variance.

Along with the increased HbA1c, fasting plasma glucose and oral glucose tolerance test(OGTT) 2 h glucose levels, the prevalence of c-fPWV was significantly higher (P for trend <0.0001), adjusting for age, sex, body mass index(BMI), blood pressure and lipids, c-fPWV was still along with the increased HbA1c( P for trend =0.004). In addition, HbA1c significantly interacted with age to affect c-fPWV (P for interaction<0.0001). The association was stronger in subjects who were elder (≥60 yrs;P for trend=0.004) and had higher blood pressure (systolic blood pressure≥140 mm Hg(1 mm Hg=0.133 kPa) and(or) diastolic blood pressure ≥90 mm Hg (P for trend=0.028)).

In non-diabetes, HbA1c is associated with arteriosclerosis which independent of metabolic risk factors. Age and blood pressure may modify the associations between HbA1c and c-fPWV.

To evaluate the association between serum γ-glutamyl transferase(GGT) and diabetic peripheral polyneuropathy(DPP) in type 2 diabetics.

From January, 2010 to December, 2011, 159 cases of type 2 diabetics were enrolled randomly from the endocrine department of our hospital. Height, weight, fasting blood glucose(FBG), glycosylated hemoglobin(HbA1c), alanine aminotransferase, aspartate aminotransferase, creatinine, blood urea nitrogen, blood fat were detected in all patients. Patients were divided into two groups(DPP, non-DPP) accordinging to Michigan Neuropathy Screening Instrument (MNSI) and nerve conduction velocity(NCV) examinations. There were 82 patients in the DPP group with a mean age of (57±13) yrs, 77 patients in the non-DPP group with a mean age of (56±12) yrs. All patients were also divided into two groups according to serum GGT level: group A (GGT≤50 U/L) and group B(GGT>50U/L) , and there were 115 patients in group A (mean age (56±14)yrs), 44 patients in group B(mean age (58±13) yrs). T test was implied in the comparison of data between the two groups, and the risk factors of DPP were investigated with multiple logistic regression.

The body weight((69±13) vs (66±9)kg, t=1.854, P<0.05), serum GGT ((32±25) vs (18±9)U/L,t=4.310, P<0.01), alanine aminotransferase ((24±17) vs (18±7)U/L,t=2.304, P<0.05), triglyceride ((2.5±2.0) vs (1.4±0.9)mmol/L,t=4.165, P<0.01), glycosylated hemoglobin(HbA1c) ((9.4±3.0)% vs (8.6±1.9)%,t=-1.727, P<0.05) were higher in DPP group than those in non-DPP group. Serum alanine aminotransferase, aspartate aminotransferase in patients of group A were significantly lower than those in patients of group B((16±11) vs(34±17)U/L and (17±7) vs (29±15)U/L,t=3.721, 2.669, both P<0.05). The tibial nerve motor conduction velocity, common peroneal nerve and peroneal nerve sensory conduction velocity in group A were better than those in group B((45.4±5.0) vs (40.3±5.6)m/s, (47.3±4.8) vs (40.2±5.4) m/s, and (48.4±5.1) vs (41.3±9.7)m/s, respectively;t=4.031, 4.110, 4.006, all P<0.05). Multiple logistic regression analysis implied that of the five significant variables between DPP group and non-DPP group, only serum GGT remained independently associated with the presence of DPP, which carried a relative risk with an odds ratio of 1.10(P<0.05).

It shows that increased level of serum GGT have important clinical implications in the presence of DPP, may be a risk factor of DPP in type 2 diabetes mellitus.

To investigate the mechanisms of exenatide and insulin glargine in regulating lipid metabolism of adipose tissue in diabetic rats.

Male SD rats (7-8 weeks old, 180-200 g) were randomly divided into normal chow (NC group, n=8) or high-fat diet (n=30). After 5 weeks of high-fat diet, diabetic rats were induced by low dose streptozotocin (STZ) and were randomly divided into 3 groups: untreated diabetic group (DM), exenatide - treated group (EXE group) or insulin glargine - treated group (INS group). NC and DM groups were administrated by normal saline, the other two groups were given exenatide or insulin glargine for 4 weeks initiated at the 3rd day after STZ injection. Protein expressions of phosphoenolpyruvate carbexykinase (PEPCK) and fatty acid synthase (FAS) were assayed by Western blotting. Gene expressions of PEPCK, FAS, acetyl-coA carboxylase1 (ACC-1), pigment epithelium-derived factor (PEDF), and adipose triglyceride lipase (ATGL) were quantified by real-time polymerase chain reaction(PCR). ANOVA or LSD test were used for data analysis.

Compared with NC group, the gene and protein levels of PEPCK, FAS, and ACC-1 in DM group were significantly decreased (all P<0.05), while the gene expressions of ATGL and PEDF were increased (allP<0.05). After exenatide and insulin glargine treatment, mRNA and protein levels of PEPCK, FAS, and ACC-1 were increased (allP<0.05), and mRNA levels of ATGL and PEDF were decreased (allP<0.05). Compared with INS group, the increases in the gene and protein levels of PEPCK and FAS in EXE group were greater (PEPCK mRNA with EXE vs INS group: 1.68±0.45 vs 1.15±0.24; FAS mRNA: 7.12±0.13 vs 1.18±0.16; PEPCK protein (1.11±0.08) vs (0.87±0.08), FAS protein (1.95±0.10) vs ( 0.99±0.08),t=2.525, 69.374, 5.312, 18.670, all P<0.05).

Exenatide and insulin glargine treatment can ameliorate ectopic lipid deposition by increasing lipid synthesis and decreasing lipolysis of adipocytes in diabetic rats, in which exenatide has greater effect on triglyceride synthesis.

To investigate the protective effects of atorvastatin on the renal damage induced by glycated bovine albumin (GBA) in rats.

Forty healthy male SD rats (weight 230-250 g) were randomly assigned to 4 groups according to random number table: the normal diet group, high fat diet group (fed on high fat diet), GBA group (intraperitoneally-injected with GBA 40 mg·kg^-1·d^-1, fed on high fat diet) and GBA+ atorvastatin group (intraperitoneally-injected with GBA 40 mg·kg^-1·d^-1, orally administrated atorvastatin 20 mg·kg^-1·d^-1, and fed on high fat diet), 10 rats in each group. After 24 weeks, serum advanced glycation end products (AGEs) level was determined by using enzyme linked immunosorbent assay. The expression of the receptor of AGEs (RAGE) mRNA was determined by real-time polymerase chain reaction. The expression of S100 (a kind of AGEs) and RAGE protein in kidney was determined by immunohistochemical analysis. The area of glomerulus and mesangial region of the kidney were measured. Statistical analysis was performed by using one-way ANOVA and t test.

There were no differences in serum glucose, total cholesterol and creatinine levels among the 4 groups (F=1.780, 2.012, 2.075, all P>0.05). Compared with that in high fat diet group, serum AGEs level was significantly increased in GBA group((72±4) vs (50±5)μg/L,t=3.445, P<0.05); glomerular hypertrophy and mesangial expansion were more serious (glomerular area: (9505±326) vs (7920±518)μm^2,t=2.587, P<0.05; mesangial area: (5751±316) vs (1898±259)μm^2,t=9.435, P<0.05); and the expression of the RAGE mRNA in the kidney was significantly increased(9.7±1.0 vs 2.4±0.5,t=6.629, P<0.05), whereas the expression of S100, RAGE protein of kidney increased in GBA group. Compared with GBA group, the glomerular hypertrophy, mesangial expansion were significantly ameliorated in GBA+ atorvastatin group(glomerular area: (7276±326) vs (9505±326)μm^2,t=4.834, P<0.05; mesangial area: (2436±316) vs (5752±316)μm^2,t=7.418, P<0.05); the serum AGEs level and the RAGE mRNA expression of kidney were significantly lower (AGEs: (53±3) vs (72±4)μg/L,t=3.298, P<0.05; RAGE mRNA: 3.3±0.8 vs 9.7±1.0,t=4.978, P<0.05), whereas the expression of S100, RAGE protein decreased in the atorvastatin treatment group.

Protection effects of atorvastatin on renal damage induced by AGEs may be mediated by decreased AGEs and lower expression of RAGE.

Obesity, especially abdominal obesity, is a high risk factor for type 2 diabetes, hypertension, lipid metabolism disorders and atherosclerosis^[1]。 More than 80% of patients with type 2 diabetes mellitus are combined with overweight and obesity, which is the first factor of cardiovascular and cerebrovascular death^[2]。 Traditional hypoglycemic drugs such as sulfonylureas, insulin and thiazolidinediones can lead to weight gain while lowering blood sugar through different mechanisms, thus aggravating insulin resistance, often leading to failure of blood sugar control and increasing the risk of cardiovascular and cerebrovascular events^[3]。

Oral hypoglycemic drugs are one of the current treatments for type 2 diabetes mellitus (T2DM). As the most commonly used oral hypoglycemic drugs, sulfonylureas have been in clinical use for more than 50 years. They have a fast onset of action and are strongly tolerated by patients, but their efficacy varies greatly among different individuals. In addition to the impairment of pancreatic islet β cell function, baseline glucose level and severity of insulin resistance in different individuals, the differences in genetic background of patients are also one of the reasons for different curative effects. Pharmacogenomics is a new discipline developed on the basis of pharmacogenetics. It is the product of the combination of molecular pharmacology and functional genomics, which can further explain the reasons for the differences in drug efficacy at the molecular level. It mainly studies the effects of single nucleotide polymorphisms (SNPs) of drug metabolism, transport and drug action receptor-related genes on drug efficacy. Candidate genes mainly include drug metabolizing enzymes, drug transporters and drug receptor genes. By exploring the influence of diversity of these genes on drug efficacy and adverse reactions, we can guide clinical individualized treatment, select the best drug types and dosages, improve the drug efficacy of different individuals, and minimize the occurrence of adverse drug reactions. This paper mainly introduces the research progress of pharmacogenomics of sulfonylureas.

Blood glucose monitoring is an important part of diabetes management. The results of blood glucose monitoring are helpful to judge the degree of glucose metabolism disorder in patients, formulate hypoglycemic schemes, reflect the effect of hypoglycemic treatment and guide the adjustment of treatment schemes. The dynamic blood glucose monitoring (CGM) technology developed in recent years can provide continuous, comprehensive and reliable blood glucose information throughout the day, review the trend of blood glucose fluctuations, and find hyperglycemia and hypoglycemia that are not easily detected by traditional monitoring methods. Therefore, CGM technology has been widely popularized and applied in clinical practice.

The American Diabetes Society/European Diabetes Association, an authoritative academic body on diabetes, issued a new position statement in April 2012, emphasizing the "patient-centered" treatment philosophy and further emphasizing the role of basal insulin in the treatment of diabetes. Neutral protamine insulin (NPH), a basal insulin that has been widely used before, has the limitations of relatively short action time, obvious peak action and hypoglycemia, etc. However, new insulin analogues have made up for these deficiencies in recent years. As a long-acting insulin analogue, insulin detemir is closer to physiological basal insulin secretion. It can effectively control blood sugar, reduce blood sugar variation in individuals, reduce the risk of hypoglycemia, and reduce weight gain caused by insulin therapy. It is also safe and effective in the elderly, children and gestational diabetes patients.

High-density lipoprotein cholesterol (HDL-C) reduction has been considered a major risk factor for diabetic macrovascular atherosclerosis, but its association with diabetic microvascular disease is poorly understood. The purpose of this study was to investigate whether it is related to diabetic microvascular complications.

The incidence of microalbuminuria in diabetic patients is 40%, and it has been used as a predictor of diabetic nephropathy. In addition, microalbuminuria was found to be associated with cardiovascular disease and death in diabetic and non-diabetic patients. The American Heart Association recommends that patients with diabetes and hypertension be tested for microalbuminuria to assess their cardiovascular risk. Studies from Brazil investigated the predictive value of randomized urinary albumin levels in the development of cardiovascular events, diabetic nephropathy and death in patients with type 2 diabetes.

Several studies have shown that nonalcoholic fatty liver disease is associated with the occurrence of cardiovascular events. However, it is not clear whether fatty liver, insulin resistance (IR) and metabolic syndrome are related to coronary atherosclerosis, and whether they are independent of other cardiovascular risk factors is also unknown. Researchers from South Korea explored them.

Pharmacokinetic studies have demonstrated that persistent platelet hyperreactivity remains prevalent in diabetic patients despite clopidogrel treatment. Clinical trials have not definitively confirmed whether clopidogrel is comparable in efficacy in diabetic and non-diabetic patients.