Effect of oral antidiabetic agents on plasma amylin level in patients with non-insulin-dependent diabetes mellitus (type 2).

The purpose of the study was the comparison of the effect of the oral therapy of non-insulin-dependent diabetes mellitus (NIDDM) with either a sulphonylurea or biguanide derivative on plasma amylin level. In 10 healthy individuals the fasting plasma amylin level was 1.56 +/- 0.27 pmol/l (mean +/- SEM) and 6 min after i.v. injection of 1 mg glucagon a fourfold increase was observed. In 10 patients with NIDDM receiving glibenclamide (CAS 10238-21-8) the fasting plasma amylin level was twofold higher than in healthy control (2.72 +/- 0.38 pmol/l; p < 0.025) but following glucagon administration it increased only twofold. In 15 patients treated with metformin (CAS 657-24-9) the fasting plasma amylin level was similar to that in healthy individuals (1.64 +/- 0.25 pmol/l), but after glucagon stimulation the increment of plasma amylin was minimal and the relevant mean value was significantly lower when compared with those in healthy individuals and with NIDDM patients treated with glibenclamide. In 10 untreated obese patients with newly diagnosed NIDDM the administration of glibenclamide (14 days) resulted in the increase of basal (2.47 +/- 0.23 and 3.16 +/- 0.29 pmol/l; p < 0.1), and glucagon stimulated (3.34 +/- 0.39 and 4.56 +/- 0.38; p < 0.05) plasma amylin concentrations, whereas other 10 patients receiving metformin showed a decrease in fasting plasma level of this peptide before (2.64 +/- 0.59 and 1.28 +/- 0.38 pmol/l; p < 0.1), and after glucagon injection (5.02 +/- 0.55 and 2.83 +/- 0.65 pmol/l; p < 0.02). With the respect to the trophic effect of amyloid deposits in the pancreatic islets and to a hypothetic effect of amylin increasing insulin resistance, the present results emphasize the particular usefulness of metformin in the pharmacological treatment of NIDDM. All contraindications and side effects of metformin should be taken into account before drug administration.     

The Pharmaceutical care of patients with type 2 diabetes mellitus

Objective To evaluate the efficiency of pharmaceutical care on the control of clinical parameters, such as fasting glycaemia and glycosylated haemoglobin in patients with Type 2 Diabetes mellitus. Setting This study was conducted at the Training and Community Health Centre of the College of Medicine of Ribeirao Preto, University of Sao Paulo, Brazil. Methods A prospective and experimental study was conducted with 71 participants divided in two groups: (i) pharmaceutical care group (n=40), and (ii) the control group (n=31). The distribution of patients within these groups was made casually, and the patients were monitored for 12 months. Main outcome measure: Values for fasting glycaemia and glycosylated haemoglobin were collected. Results Mean values of fasting glycaemia in the pharmaceutical care group were significantly reduced whilst a small reduction was detected in the control group at the same time. A significant reduction in the levels of glycosylated haemoglobin was detected in patients in the pharmaceutical care group, and an average increase was observed in the control group. Furthermore, the follow-up of the intervention group by a pharmacist contributed to the resolution of 62.7% of 142 drug therapy problems identified. Conclusion In Brazil, the information provided by a pharmacist to patients with Type 2 Diabetes mellitus increases compliance to treatment, solving or reducing the Drug Therapy Problem and, consequently, improving glycaemic control.     

Tighter control of postprandial hyperglycemia with mitiglinide/voglibose fixed-dose combination in Japanese patients with type 2 diabetes mellitus

Objective: The objective of this study was to compare the effects of mitiglinide, voglibose and its combination on metabolic responses after a test meal in Japanese patients with type 2 diabetes mellitus (T2DM).

Research design and methods: This randomized crossover study consisted of four periods between August and November 2011. In the first period, all patients (n = 12) received water alone (control period). In the next three periods, the patients received 10 mg mitiglinide, 0.2 mg voglibose or a combination in a random order.

Main outcome measures: Postprandial metabolite/hormone levels were then measured.

Results: Plasma glucose and serum insulin reached peak levels by 60 – 90 and 90 min, respectively, after the test meal in the control group. The combination reduced postprandial glucose levels compared with mitiglinide or voglibose alone, particularly at 30 – 90 min, which significantly exceeded the effects of mitiglinide (p < 0.05). Mitiglinide and the combination restored early insulin response, whereas the combination provided an insulin-sparing effect compared with mitiglinide alone. The combination improved postprandial lipid profiles, combining the effects of both drugs.

Conclusion: This study revealed marked differences in the postprandial metabolic effects of mitiglinide, voglibose and its combination in patients with T2DM. The combination therapy should enable tighter control of postprandial hyperglycemia compared with the individual drugs.     

格列美脲治疗2型糖尿病伴肥胖患者的临床效果及药理分析

目的 探讨2型糖尿病伴肥胖患者施以格列美脲治疗的临床效果,并作药理分析。方法 46例2型糖尿病伴肥胖患者,根据随机数字表法分为观察组和对照组,每组23例。对照组患者给予格列吡嗪缓释片治疗,观察组患者给予格列美脲片治疗。比较两组患者治疗前后血糖指标[空腹血糖(FPG)、餐后2 h血糖(2 h PG)、空腹胰岛素(FINS)、糖化血红蛋白(HbA1c)]、血脂[总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)]及体质量指数(BMI)。结果 治疗后,观察组患者FPG、2 h PG、FINS、HbA1c水平分别为(6.04±0.43)mmol/L、(11.12±2.52)mmol/L、(657.84±10.37)pmol/L、(6.46±0.58)%,均低于对照组的(7.45±0.27)mmol/L、(14.24±2.09)mmol/L、(704.29±11.09)pmol/L、(8.53±0.79)%,差异均具有统计学意义(P<0.05)。观察组患者TC、TG、LDL-C、BMI水平分别为(3.24±0.79)mmol/L、(1.88±0.69)mmol/L、(1.96±0.48)mmol/L、(23.05±2.55)kg/m2,均低于对照组的(4.75±0.38)mmol/L、(2.35±0.75)mmol/L、(2.95±0.66)mmol/L、(27.76±4.10)kg/m2,差异均具有统计学意义(P<0.05)。结论 以格列美脲治疗2型糖尿病伴肥胖患者,可使患者血糖及血脂水平得以有效控制,同时可减轻其肥胖程度,具较高应用价值。     

Cinnamon supplementation in patients with type 2 diabetes mellitus

Diabetes mellitus is the sixth leading cause of death in the United States, and most patients with the disease have type 2 diabetes. The effectiveness of cinnamon supplementation in patients with type 2 diabetes has received a great deal of media attention after a study was published in 2003. Although the efficacy of cinnamon in patients with diabetes has not been established, many patients seek other therapies and supplement their prescribed pharmacologic therapy with cinnamon. We conducted a literature search, limited to English-language human studies, using MEDLINE (1966-August 2006), EMBASE (1980-August 2006), International Pharmaceutical Abstracts (1970-August 2006), and Iowa Drug Information Service (1966-August 2006). References from articles and clinical trials were reviewed for additional sources; no abstracts were reviewed. We found two prospective, randomized, double-blind, placebo-controlled, peer-reviewed clinical trials and one prospective, placebo-controlled, peer-reviewed clinical trial that evaluated the efficacy of cinnamon supplementation in patients with type 2 diabetes; a total of 164 patients were involved in these trials. Two of the studies reported modest improvements in lowering blood glucose levels with cinnamon supplementation in small patient samples. One trial showed no significant difference between cinnamon and placebo in lowering blood glucose levels. Overall, cinnamon was well tolerated. These data suggest that cinnamon has a possible modest effect in lowering plasma glucose levels in patients with poorly controlled type 2 diabetes. However, clinicians are strongly urged to refrain from recommending cinnamon supplementation in place of the proven standard of care, which includes lifestyle modifications, oral antidiabetic agents, and insulin therapy.     

2型糖尿病患者运动依从性的研究进展

运动作为预防2型糖尿病发生与进展的重要手段之一,患者的运动依从性受到多种可控或不可控的因素影响,其干预和管理手段也逐渐向数字化方向发展。本文针对2型糖尿病患者运动依从性现状进行综述,剖析其运动依从性的主要影响因素,并提出相应改善2型糖尿病患者运动依从性的干预对策,为2型糖尿病患者运动行为促进提供参考。     

The effect of hyperglycaemia on the absorption of glibenclamide in patients with non-insulin-dependent diabetes mellitus

We have studied the absorption of glibenclamide 10 mg as a single morning dose in 7 patients with non-insulin-dependent diabetes mellitus, comparing normoglycaemic and hyperglycaemic states.The maximal glibenclamide plasma concentrations were significantly higher in the normoglycaemic than in the hyperglycaemic state (448 vs 228 mg·1^-1) and these peak concentrations were attained faster in normoglycaemia than in hyperglycaemia (3.7 vs 5 h).We conclude that the absorption of glibenclamide in the two states is different.     

Disruption of estrogen-regulated gene expression by dioxin: downregulation of a gene associated with the onset of non-insulin-dependent diabetes mellitus (type 2 diabetes)

Expression of an estrogen-regulated reporter gene, growth of MCF-7 cells in the presence of 17beta-estradiol (E2) or E2 plus TCDD, and DNA microarray plus real time quantitative PCR analyses of gene expression in MCF-7 cells were used to evaluate the effects of TCDD, a known E2 antagonist, on E2-regulated gene expression in human cells. TCDD added simultaneously with E2 exhibited significantly decreased E2-associated upregulation of reporter gene expression compared with cells treated with E2 alone, and decreased E2 enhancement of mitosis in MCF-7 cells. MCF-7 cells treated with E2 or E2 plus TCDD and DNA microarray-evaluated to determine patterns of gene expression, showed substantial differences in gene expression in TCDD-treated cells compared with E2-treated cells. Of the 2400 genes on the Perkin Elmer global array microchip utilized for this analysis, a minimum of 317 were significantly upregulated and 488 were significantly downregulated. Of these, the gene encoding insulin receptor substrate-1 (IRS-1), the protein product of which has been previously reported to be decreased, missing, altered, or defective in persons with type 2 diabetes mellitus, was evaluated by real time quantitative PCR to corroborate the array data. An evaluation of the potential consequences of TCDD-altered IRS-1 downregulation is presented.     

The use of insulin in elderly patients with type 2 diabetes mellitus

Introduction: Older patients with diabetes sometimes present comorbidities that increase the risk of other common geriatric syndromes. In such patients, treatment with insulin is usually started when full doses of oral hypoglycemic agents are no longer adequate to achieve acceptable glycemic control.

Areas covered: This article reviews the available literature on the use of insulin in elderly patients with type 2 diabetes. The aims are to gain information on: the benefits and risks of initiating insulin treatment, the efficacy and safety of different types of insulin and the most appropriate initial dosing and titration regimens. Thirteen published trials have evaluated the effects of different insulin regimens in the management of elderly subjects with type 2 diabetes but, given that older people are generally excluded in clinical studies with insulin, only three published reports on subgroup analyses are limited to elderly patients.

Expert opinion: The available literature shows that the addition of insulin to current oral treatments is generally safe and effective in improving metabolic control, with a low risk for hypoglycemia. Further research is needed to better understand the most appropriate insulin regimens necessary to achieve glycemic goals while appropriately addressing the risk of hypoglycemia.     

运动疗法对2型糖尿病患者血液流变学的影响

目的:观察运动疗法对2型糖尿病患者血液流变学的影响.方法:选择2型糖尿病患者117 例,分为运动疗法组(65 例)和非运动疗法组(52 例),两组在常规药物治疗下,运动疗法组进行运动治疗6个月,对照组不进行运动治疗,观察两组患者运动前后血液流变学指标的变化.结果:运动疗法组低切变率全血黏度、血浆黏度、红细胞聚集指数、红细胞压积下降,红细胞变形指数升高,与运动治疗前相比差异有显著性(P＜0.01),与对照组相比差异也有显著性.结论:运动疗法能有效改善2型糖尿病患者血液流变学状态.     

Prevention and current onset delay approaches of type 2 diabetes mellitus (T2DM)

The urgent need to treat type 2 diabetes mellitus (T2DM), which is currently reaching epidemic proportions, has been a major focus of healthcare systems and policy makers worldwide. Pharmacological treatment and lifestyle interventions together with the control of cardiovascular risk factors are the main strategies to prevent or delay the onset of T2DM. The present review discusses the state of the art knowledge of effective therapeutic approaches (metformin, thiazolidinediones, nateglinides, α-glucosidase inhibitors, incretin-based and angiotensin-based therapies, weight reducers, statins, fibric acid derivatives), including surgery, and identifies the major lifestyle changes for specific target groups.     

The use of insulin in elderly patients with type 2 diabetes mellitus

INTRODUCTION: Older patients with diabetes sometimes present comorbidities that increase the risk of other common geriatric syndromes. In such patients, treatment with insulin is usually started when full doses of oral hypoglycemic agents are no longer adequate to achieve acceptable glycemic control. AREAS COVERED: This article reviews the available literature on the use of insulin in elderly patients with type 2 diabetes. The aims are to gain information on: the benefits and risks of initiating insulin treatment, the efficacy and safety of different types of insulin and the most appropriate initial dosing and titration regimens. Thirteen published trials have evaluated the effects of different insulin regimens in the management of elderly subjects with type 2 diabetes but, given that older people are generally excluded in clinical studies with insulin, only three published reports on subgroup analyses are limited to elderly patients. EXPERT OPINION: The available literature shows that the addition of insulin to current oral treatments is generally safe and effective in improving metabolic control, with a low risk for hypoglycemia. Further research is needed to better understand the most appropriate insulin regimens necessary to achieve glycemic goals while appropriately addressing the risk of hypoglycemia.     

Case-control study in non-insulin-dependent diabetes mellitus (NIDDM) subjects treated with acarbose

Newer therapeutic approaches are being employed for the treatment of diabetes mellitus, and among these, acarbose, an α-glucosidase inhibitor, has proven effective in lowering postprandial blood glucose levels and glycosylated hemoglobin. The aim of the present study was to evaluate the effects of acarbose in non-insulin-dependent diabetes mellitus (NIDDM) patients. Thirty-four NIDDM outpatients were enrolled who were followed at our Diabetic Clinic of the Internal Medicine Institute—Chieti University. They were randomized according to a case-control study protocol. The observation period lasted 3 months and tests were performed on the first, second, and third month. Group 1 patients received acarbose 50 mg, three times a day for the first month and 100 mg three times a day for the remaining 2 months. Subjects treated with acarbose showed a reduction of 22% in blood glucose (BG) (P < 0.001) and of glycosylated hemoglobin (HbA1c) (17%-P < 0.001) at the end of the study, while the control subjects presented only a slight reduction (10%) of BG (P < 0.05). After case-control analysis, BG and HbA1c were significantly lower in the case subjects (P < 0.005 and P < 0.02, respectively). In patients with NIDDM, acarbose is a well-tolerated drug with short-term effects mainly on blood glucose levels, while the lowering effects on HbA1c require longer observation periods. Drug Dev. Res. 43:128–131, 1998. © 1998 Wiley-Liss, Inc.     

2型糖尿病合并贫血的相关分析

目的评估2型糖尿病患者贫血的影响因素。方法本研究为病例对照研究,108例患者被分为两组:贫血组54例糖尿病合并贫血患者,非贫血组为54例糖尿病不伴贫血患者,从临床和实验室收集资料。结果贫血患者的年龄、糖尿病病程、肌酐、C反应蛋白、尿蛋白明显高于非贫血患者,白蛋白水平、肌酐清除率明显低于贫血患者;血红蛋白与白蛋白、肌酐清除率正相关;与糖尿病病程、肌酐、CRP、尿蛋白、年龄负相关;多元回归分析显示:白蛋白、肌酐清除率、尿蛋白、糖尿病病程是血红蛋白的浓度的影响因子;Logistic回归分析显示:白蛋白、肌酐清除率、尿蛋白、糖尿病病程也是糖尿病患者贫血影响因素。结论贫血是多因素的结果,白蛋白、肌酐清除率、尿蛋白、糖尿病病程、微炎症反应等因素不同程度地影响血红蛋白浓度。     

Pathogenesis of non-insulin-dependent (type II) diabetes mellitus (NIDDM) - genetic predisposition and metabolic abnormalities

Non-insulin-dependent diabetes mellitus (NIDDM), also known as type II diabetes, is characterized by abnormal glucose homeostasis, resulting in hyperglycemia, and is associated with microvascular, macrovascular, and neuropathic complications. NIDDM is a complex disease with many causes. Both genetic and environmental factors play important roles in the pathogenesis of NIDDM. Cumulative evidence on the high prevalence of NIDDM in certain ethnic groups, the high concordance rate for the disease in monozygotic twins, familial aggregation, and familial transmission patterns suggests that the genetic component plays an important etiological role in the development of NIDDM. In genetically predisposed individuals, there is a slow progression from a normal state to hyperglycemia, largely due to a combination of insulin resistance and defects in insulin secretion. Although numerous candidate genes responsible for insulin resistance and for the defects in insulin secretion have been reported, no specific gene(s) accounting for the majority of cases of the common type of NIDDM has been identified. Considerable evidence indicates that environmental and other factors, including diet, stress, physical activity, obesity and aging, also play an important role in the development of the disease. In conclusion, the pathogenic process of NIDDM depends on a complex interaction between genetic and environmental factors.     

The treatment of type 1 diabetes mellitus with agents approved for type 2 diabetes mellitus

Introduction: The management of type 1 diabetes remains a challenge for clinicians. Current practice is to administer insulin analogues to best mimic normal physiological insulin profiles. However, despite our best efforts the majority of individuals with type 1 diabetes continue to suffer from suboptimal glucose control, significant hypoglycemia and microvascular tissue complications of the disease. There is thus a significant unmet need in the treatment of T1DM to obtain better glycemic control.

Areas covered: We discuss the use of α-glucosidase inhibitors, dipeptidyl-peptidase inhibitors, glucagon-like peptide 1 agonists, biguanides, thiazolidinediones and sodium glucose co-transporter 2 inhibitors in individuals with T1DM.

Expert opinion: Non-insulin therapies present a unique and exciting adjunctive treatment for individuals with type 1 diabetes. Although data are scarce, the classes of medications discussed help to lower glucose, decrease glycemic excursions and in some cases improve body weight, along with allowing dose reductions in total daily insulin. Glucagon-like peptide 1 agonists and sodium glucose co-transporter 2 inhibitors, in particular, have been demonstrated to provide clinical improvements in individuals with T1DM and we feel their use can be explored in obese, insulin-resistant patients with T1DM, those with frequent and significant glycemic excursions or individuals with persistently elevated hemoglobin A1c.     

2型糖尿病合并高血压病的抗高血压药物治疗

糖尿病慢性并发症是糖尿病患者致死、致残的主要原因。在占临床糖尿病病例90％～95％以上的2型糖尿病患者中，最常见且危害最大的慢性并发症是心血管疾病，尤其是高血压病。因此，针对2型糖尿病患者合并的高血压病，早期、及时和达标治疗非常必要。由于糖尿病本身代谢紊乱和病理生理变化的影响，使得糖尿病合并的高血压病具有一些临床特点，临床医生在降压方案的确定和降压药物的选择时，应当注意这些特点。     

Managing hypertension in patients with type 2 diabetes mellitus.

PURPOSE: Current guideline recommendations for effective strategies to optimize the treatment of patients with concomitant hypertension and type 2 diabetes mellitus are reviewed. SUMMARY: Current estimates indicate that 20 million people in the United States have diabetes, 90-95% of whom have type 2 diabetes mellitus. Type 2 diabetes mellitus is associated with an increased risk of premature death from cardiovascular disease (CVD), stroke, and end-stage renal disease. Hypertension is an extremely common comorbidity in patients with type 2 diabetes mellitus. The coexistence of hypertension in patients with type 2 diabetes is particularly destructive because of the strong linkage of the two conditions with CVD, stroke, progression of renal disease, and diabetic nephropathy. Current guidelines, including those issued by the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure, the National Kidney Foundation, and the American Diabetes Association, provide evidence-based recommendations for the treatment of hypertension in patients with type 2 diabetes mellitus. However, studies indicate that guidelines are not widely followed. Therefore, the beneficial effects of appropriate hypertension treatment observed in clinical trials are often not recognized in clinical practice. Pharmacists are ideally positioned to help improve guideline implementation and patient outcome. CONCLUSION: Pharmacists must become more vigilant about following current guidelines for the treatment of patients with concomitant hypertension and type 2 diabetes mellitus. Strategies such as patient education and medication assessment can help to optimize care for these patients and slow the progression to diabetic nephropathy.