Measurement of bone mineral density in patients with type 2 diabetes mellitus

AIM：To investigate into the changes in bone mineral density (BMD) in patients with Type 2 diabetes mellitus.METHODS:BMD of lumbar vertebrae 2-4 and femur in 63 cases of patients with type 2 diabetes mellitus were measured with dual energy X-ray absorptiometry (DEXA) and were compared with age, sex and BMI-matched normal control group. RESULTS:No significant differences were found in BMD of lumbar vertebrae 2-4 in female of menopause with Type 2 diabetes mellitus(P&;gt;0.05), but BMD of total were lower than that of the controls (P&;lt;0.05), BMD of neck were significantly lower than that of the controls (P&;lt;0.01); No significant differences were found in BMD of L2-4 and femur in male of 50 years old above with Type 2 diabetes mellitus (P&;gt;0.05). CONCLUSION:BMD of Type 2 diabetes mellitus is different according to different sex,BMD of female of menopause with type 2 diabetes mellitus were descended easily,especially in areas of neck BMD, it should couse to pay attention to in order to prevent pathologic bone fracture;BMD of male of 50 years old above with Type 2 diabetes mellitus have no the obvious changes than that of the controls.     

Does serum cystatin C level reflect insulin resistance in patients with type 1 diabetes?

ObjectivesThe aim of study was to evaluate the relationship between serum cystatin C and insulin resistance (IR) in type 1 diabetic patients being the participants of Poznan Prospective Study.Design and methodsThe study was performed on 71 Caucasian patients (46 men); with type 1 diabetes, who were recruited into the Poznan Prospective Study, at the age of 39 ± 6.1 meanly, and treated with intensive insulin therapy since the onset of the disease. The follow-up period and diabetes duration were 15 ± 1.6 years. Insulin resistance (IR) was assessed by estimated glucose disposal rate (eGDR) calculation with cut-off point 7.5 mg/kg/min. Patients were divided into two groups, according to the presence or absence of IR.ResultsFrom among 71 patients, 31 patients (43.7%) presented decreased sensitive to insulin with eGDR below 7.5 mg/kg/min. Patients who had eGDR < 7.5 mg/kg/min (insulin resistant), compared with subjects with eGDR > 7.5 mg/kg/min (insulin sensitive), had higher level of serum cystatin C [0.59 (IQR:0.44–0.84) vs 0.46 (IQR:0.37–0.55) mg/L, p = 0.009]. A significant negative correlation between cystatin C and eGDR was revealed (Rs = − 0.39, p = 0.001). In regression model cystatin C was related to insulin resistance, adjusted for sex, BMI, eGFR and duration of diabetes [OR 0.03 (0.001–0.56), p = 0.01].ConclusionsHigher level of serum cystatin C is related to decreased insulin sensitivity in patients with type 1 diabetes. This relationship seems to have an important clinical implication.     

Is postprandial hypertriglyceridaemia in relatives of type 2 diabetic subjects a consequence of insulin resistance?

BACKGROUND: Higher postprandial triglyceride responses reported in first degree relatives of people with type 2 diabetes (REL) were postulated to be the result of an early, possibly intrinsic, defect in oral lipid handling. The postprandial triglyceride response to high fat meals (HFM) in normal subjects is reduced by the insulin response to dietary carbohydrate (CHO) in the meal. The aims of this study were to examine whether (1) insulin resistance is associated with an intrinsic defect in triglyceride handling in insulin-resistant REL and (2) insulin resistance is associated with altered triglyceride handling after HFM with high CHO content. MATERIALS AND METHODS: Postprandial responses to a HFM in normolipidaemic, normoglycaemic REL were compared with subjects without a family history of diabetes mellitus (CON). Over 6 h, the insulin, glucose, triglyceride and nonesterified fatty acid (NEFA) responses after a high fat (80 g fat), low CHO (HFM-LC; 20 g CHO, 4250 kJ) meal and a high fat, high CHO (HFM-HC; 100 g CHO, 5450 kJ) meal were examined. RESULTS: The 10 (7F/3M) REL were significantly more insulin-resistant, determined by glucose infusion during a hyperinsulinaemic euglycaemic clamp than the 10 (5F/5M) CON (glucose infusion rate 44.6 +/- 4.9 vs. 60.0 +/- 4.8 micromol min(-1) kg FFM(-1), P = 0.037). Subjects were similar for age and body mass index (BMI). The triglyceride increments after the HFM-LC were similar in both, peaking at 180-240 min (Delta0.77 +/- 0.11 mmol L(-1)), demonstrating no postprandial defect in REL, despite insulin resistance. There was a significantly lower postprandial triglyceride response in CON following the HFM-HC compared with the HFM-LC, but not in REL. In contrast, the higher insulin level during the HFM-HC was associated with significantly greater NEFA level suppression than in the HFM-LC (2.13 +/- 0.51 vs. 0.70 +/- 0.35 mmol L(-1), P = 0.03), only in the REL. CONCLUSIONS: These results are inconsistent with a primary aetiological role for postprandial hypertriglyceridaemia in already insulin resistant type 2 diabetic REL, but raise the possibility that this potentially atherogenic manifestation is secondary to insulin resistance lessening VLDL production and/or release from the liver.     

Obviating much of the need for insulin therapy in type 2 diabetes mellitus: A re-assessment of insulin therapy’s safety profile

Current processes of care for diabetes mellitus (DM) were shaped during the era when insulin therapy was considered inexorable to the management of advanced stage type 2 (T2DM), though this no longer appears to be categorically true. There are also dashed hopes that insulin therapy can prevent or stall diabetes. While exogenous insulin remains a life-sparing tool for fully insulin-dependent DM, insulin therapy-induced hyperinsulinemia now appears to contribute to serious safety issues beyond hypoglycemia and weight gain. Iatrogenic and compensatory hyperinsulinemia are metabolic disruptors of β-cells, liver, muscle, kidney, brain, heart and vasculature, inflammation, and lipid homeostasis, among other systems. This may compromise β-cells, exacerbate insulin resistance (IR), and increase risk of cardiovascular (CV) disease. Striking associations between exogenous insulin and risks of CV events, cancer, and all-cause mortality in clinical trial and real-world cohorts caution that insulin may pose more harm than previously evidenced. At our disposal are numerous alternate tools that, alone or in combination, efficaciously manage hyperglycemia and glucolipotoxicity, and do so without inducing hypoglycemia, weight gain, or hyperinsulinemia. Moreover, these new tools support true precision therapy, as modern day drug classes can be aligned with the various mediating pathways of hyperglycemia at work in any given patient. Some also appear to promote β-cell survival, with intriguing data being presented for newer agents, such as incretins. As such, we encourage preferential use of non-insulin antidiabetic agents to injected insulin for the management of non-insulin-dependent patients with T2DM, including in advanced stage T2DM. The goal of this article is to augment existing literature to 1) correct misconceptions on the rationale and necessity for insulin therapy in T2DM, 2) discuss emerging negative safety data with insulin therapy, and, 3) offer a practical means to reduce reliance on insulin through delayed initiation, minimized dose, and, drug switching to safer agents, and, potentially, reframes processes of care.     

Sustained postprandial decrease in plasma levels of LDL cholesterol in patients with type‐2 diabetes mellitus

Objective. Low density lipoprotein cholesterol (LDL‐C) is an independent and modifiable risk factor for development of cardiovascular disease (CVD). Postprandial lipid metabolism has been linked to CVD, but little is known about the postprandial LDL‐C profile in patients with type‐2 diabetes (T2DM). We aimed to study the postprandial levels of LDL‐C in T2DM patients. Material and methods. After an overnight fast, 74 T2DM patients, mean age approximately 60 years, were served a standard fat‐rich meal of 3,515 kJ containing 54?% fat, 13?% protein and 33?% carbohydrates. Only drinking water was allowed postprandially. Blood samples were drawn at times 0 (fasting), 1.5, 3.0, 4.5 and 6.0?h (postprandial). In all samples, LDL‐C was measured with modified beta quantification (separation by ultracentrifugation followed by measurement of infranate high density lipoprotein cholesterol (HLD‐C) using a homogeneous assay). Results. At all postprandial times, levels of LDL‐C showed highly significant (p<0.005) decreases compared to time 0 (mean [95?% CI] maximum change in LDL‐C levels at 3.0?h: ?0.16?mmol/L [?0.12; ?0.20]; p<0.001). Independently of fasting LDL‐C levels and ongoing statin therapy, LDL‐C decreased significantly more in female compared to male patients postprandially (mean [95?% CI] maximum unadjusted change versus time 0 in LDL‐C for men [n = 56] at 3.0?h: ?0.14?mmol/L [?0.19; ?0.10], p<0.001; for women [n = 18] at 4.5?h: ?0.26?mmol/L [?0.35; ?0.18], p<0.001; ?0.14?mmol/L [?0.24; ?0.05], p = 0.005 between genders for the mean [95?% CI] fasting adjusted difference at 4.5?h in the change versus time 0 in LDL‐C; gender by time interaction: p = 0.007 (repeated measures mixed model)). Conclusions. In T2DM patients served a fat‐rich meal, levels of LDL‐C decreased significantly more in women compared to men postprandially, irrespective of fasting levels or ongoing statin therapy. This might have implications in the atherosclerotic process and on any difference in the risk of CVD between genders.     

Improvement of glycemic control after a 3–5 day insulin infusion in type 2-diabetic patients with insulin resistance can be maintained with glitazone therapy

INTRODUCTION: Insulin resistance is a common problem in obese patients with type 2 diabetes. In a prospective randomized study, we investigated the improvement of metabolic control after a 3-5 day period of intravenous insulin infusion in poorly insulin-treated, overweight type 2-diabetic patients with and without additional glitazone therapy. METHODS: Twenty-eight overweight patients (BMI > 28) with poorly insulin-treated type 2 diabetes (HbA1c > 8%) requiring > 80 IU insulin/day received a continuous insulin infusion for 3-5 days (initially 4-6 IU insulin/hour). Thereafter, 14 of the patients also received pioglitazone (15 mg/day). The two groups were compared for HbA1c, mean blood glucose (MBG), body weight, cholesterol, triglycerides and insulin requirement (IU/day) three months before insulin infusion, during infusion, and at three and six months after the infusion. RESULTS: Glycemic control was immediately improved under insulin infusion in both groups: MBG was reduced from 188 +/- 32 mg/dl at baseline to 142 +/- 28 mg/dl at the end of insulin infusion (p < 0.05). In the group receiving pioglitazone, the mean HbA1c three months after the insulin infusion was 16% lower and after six months 17% lower than baseline values (p < 0.02). Concomitantly, the required insulin dose decreased significantly by 15% after three months and 18% after six months (p < 0.02). Two patients (14%) were non-responders (< 10% reduction of required insulin dose). In the group without pioglitazone the mean HbA1c level three months after insulin infusion was 10% lower (p < 0.05) than at baseline; at six months the HbA1c value was the same as that before the infusion. The required insulin dose was 10% lower after three months and only 3% lower after six months (NS). Four patients (28%) were non-responders. DISCUSSION: Short-term insulin infusion therapy is effective in improving metabolic control and, concomitantly, in reducing insulin requirement in poorly insulin-treated type 2-diabetic patients; however, these effects are mostly limited to three months. With additional glitazone treatment after the insulin infusion, the improvement in metabolic control and the reduced insulin requirement can be maintained for more than six months.     

The serum profile of adipokines in naïve patients with diabetes mellitus type 2 and obesity

Background: The aim of this study was to explore the relationship of serum profile of adipokines with cardiovascular risk factors and anthropometric parameters in patients with diabetes mellitus type 2. Subjects: A population of 108 obese patients with DM2 was analyzed. A complete biochemical anthropometric and nutritional evaluation was performed. Results: In the analysis with leptin as a dependent variable, the IL‐6 and glucose levels remained in the model (F = 6.2; P<0.05), with an increase of 5.8 (CI 95%:2.7–7.6) ng/ml with each 1 pg/ml of IL‐6 and of 5.2 (CI95%:2.5–5.8) ng/ml with each 1 mg/dl of glucose. In a second model with adiponectin as a dependent variable, the BMI remained in the model (F = 3.77;P<0.05), with an decrease of ?3.77 (CI 95%:0.53–7.1) ng/ml with each 1 point of BMI. In the third multivariate analysis with IL‐6 as a dependent variable, the glucose level remained in the model (F = 10.1; P<0.01), with an increase of 0.09 (CI95%:0.06–0.12) pg/ml with each 1 mg/dl of glucose. In the fourth multivariate analysis with resistin as a dependent variable, the CRP remained in the model (F = 2.51; P<0.05), with an increase of 0.28 (CI 95%:0.08–0.48) pg/ml with each 1 mg/dl of CRP. Conclusion: Serum profile of adipokines is associated with different risk factors in diabetic obese patients. J. Clin. Lab. Anal. 25:409–413, 2011. © 2011 Wiley Periodicals, Inc.     

Association of thiazolidinedione with a lower risk of Parkinson’s disease in a population with newly-diagnosed diabetes mellitus

Objectives: We investigated the association of thiazolidinedione and its dose effect with the risk of Parkinson’s disease (PD) in patients with diabetes mellitus (DM).

Methods: This study enrolled 38,521 patients with newly-diagnosed DM, between 2001 and 2013, and compared them to the matched subjects without DM. The hazard ratios (HRs) for PD were compared between the thiazolidinedione-treated and non-thiazolidinedione-treated groups of the study cohort, and between subgroups who received different cumulative dosages of thiazolidinedione.

Results: We observed that 544 (1.4%) patients developed PD during the follow-up median duration of 6.2 years in patients with newly-diagnosed DM or had a higher risk for PD than patients without DM (HR?=?1.150). In the study cohort, the risk of PD was significantly lower in the thiazolidinedione-treated group (HR?=?0.399) compared to the non-thiazolidinedione-treated group. Thiazolidinedione reduced the risk of PD in a dose-dependent manner, with HRs ranging from 0.613 to 0.081 with defined daily doses of 0–90 to >720, respectively.

Conclusions: Thiazolidinedione use was associated with a significantly reduced risk of PD in patients with newly-diagnosed DM. Further studies to elucidate the common mechanism of PD and DM may provide novel therapies for these two diseases.

• Key messages

• Newly-diagnosed diabetes mellitus slightly increases the risk for Parkinson’s disease.

• Thiazolidinedione is associated with a lower risk of Parkinson's disease in a dose-dependent manner in patients with newly-diagnosed diabetes mellitus.

     

Association of the TNF-α -308G/A polymorphism with family history of type 2 diabetes mellitus in a Mexican population

AimsWe examined the possible association of the ? 308G/A polymorphism of the TNF-α promoter gene in type 2 diabetes mellitus (DM2) patients and in non-diabetic subjects with and without family history of DM2.MethodsWe studied 87 non-diabetic subjects without DM2 family history in at least one of two generations, 48 non-diabetic subjects with DM2 family history and 95 DM2 patients. Genotyping was carried out by PCR-RFLP.ResultsThe frequency of TNF-α ? 308G/A genotype was significantly lower in non-diabetic subjects without DM2 relatives (6%) as compared to DM2 patients (24%) (odds ratio (OR) = 5.24; 95% confidence interval (CI) = 1.9–15.8, p < 0.0005), but similar to non-diabetic subjects with DM2 relatives (29%) (OR = 0.77; CI = 0.3–1.7, p = 0.4). Logistic regression analysis showed the association of TNF-α ? 308G/A polymorphism with DM2 family history (OR = 5.80; CI = 1.77–18.98, p < 0.0003).ConclusionsOur results suggest that TNF-α ? 308G/A polymorphism is associated with DM2 family history and is a risk factor for DM2.     

What is the optimal dose of epinephrine during cardiopulmonary resuscitation in a rat model?

Objective

Because different species may require different doses of drug to produce the same physiologic response, we were provoked to evaluate the dose-response of epinephrine during cardiopulmonary resuscitation (CPR) and identify what is the optimal dose of epinephrine in a rat cardiac arrest model.

Methods

Rat cardiac arrest was induced via asphyxia, and then the effects of different doses of epinephrine (0.04, 0.2, and 0.4 mg/kg IV, respectively) and saline on the outcome of CPR were compared (n = 10/each group). The primary outcome measure was restoration of spontaneous circulation (ROSC), and the secondary was the change of spontaneous respiration and hemodynamics after ROSC.

Results

Rates of ROSC were 9 of 10, 8 of 10, 7 of 10, and 1 of 10 in the low-dose, medium-dose, and high-dose epinephrine groups and saline group, respectively. The rates of withdrawal from the ventilator within 60 minutes in the low-dose (7 of 9) and medium-dose epinephrine groups (7 of 8) were higher than in the high-dose epinephrine group (1 of 7, P < .05). Mean arterial pressures were comparable, but the heart rate in the high-dose epinephrine group was the lowest among epinephrine groups after ROSC. These differences in part of time points reached statistical significance (P < .05).

Conclusion

Different doses of epinephrine produced the similar rate of ROSC, but high-dose epinephrine inhibited the recovery of spontaneous ventilation and caused relative bradycardia after CPR in an asphyxial rat model. Therefore, low and medium doses of epinephrine were more optimal for CPR in a rat asphyxial cardiac arrest model.     

Buccal spray insulin (Oralgen) for type 2 diabetes: what evidence?

INTRODUCTION: The achievement of a good glycemic control and, in particular, the management of postprandial hyperglycemia represent the most significant treatment target for the management of diabetes. Multiple daily insulin injections are often still required to gain the treatment goals. Since the noncompliance with injected insulin therapy causes a slowdown in the process of glycemic compensation, novel non-injectable insulin formulations have been developed. Oral spray insulin (Oralgen) is a tasteless liquid formulation that provides insulin absorption via buccal mucosa. AREAS COVERED: To elucidate the current status of Oralgen in type 2 diabetes patients, studies of pharmacodynamic and pharmacokinetic and clinical trials are reviewed. EXPERT OPINION: The 'psychological insulin resistance,' represented by the reluctance of both patients and health-care professionals to initiate insulin therapy, could be won by alternative routes of insulin administration, improving patients' compliance. In particular, Oralgen seems to be suitable to manage the postprandial hyperglycemia without hypoglycemic risk, although no comparative studies with rapid-acting insulin analogs and no randomized controlled trials in large cohort subjects with type 2 diabetes are available to date.     

Insertion/insertion genotype of α2B-adrenergic receptor gene polymorphism is associated with silent myocardial ischemia in patients with type 2 diabetes mellitus

ObjectivesWe investigated whether α₂-adrenergic receptor (AR) polymorphisms (α_2A-AR, α_2B-AR and α_2C-AR gene) affected silent myocardial ischemia (SMI) in patients with type 2 diabetes mellitus (T2DM).Design and methodsGenetic polymorphisms were determined in 321 patients with T2DM and coronary artery disease (CAD). Among them, 129 patients experienced transient asymptomatic ST-depression during 24-hour ambulatory electrocardiogram (SMI group), and the remaining 192 patients who had ambulatory electrocardiogram-symptom matching angina were categorized as angina group.ResultsThe genotype distribution and allele frequencies of α_2B-AR gene polymorphism (insertion [I]/deletion[D]) exhibited significant difference between SMI group and angina group (both P < 0.05), with genotype II (34.9%) being higher in SMI group than in angina group (19.8%)(P < 0.01). Multivariable logistic regression analysis revealed that duration of diabetes and genotype II of α_2B-AR gene polymorphism were independently associated with SMI.ConclusionsHomozygote for I allele of α_2B-AR gene polymorphism is associated with SMI in T2DM patients with CAD.     

When glycaemic targets can no longer be achieved with basal insulin in type 2 diabetes,can simple intensification with a modern premixed insulin help? Results from a subanalysis of the PRESENT study

Aims: The aim of this analysis was to assess the efficacy and safety of intensifying insulin therapy from a basal‐only regimen to biphasic insulin aspart 30 (BIAsp 30) in patients with type 2 diabetes previously failing to reach glycaemic targets. Methods and patients: The analysis is based on data from a subpopulation of the Physicians’ Routine Evaluation of Safety and Efficacy of NovoMix^® 30 Therapy (PRESENT) study, which was a 6‐month observational study in 15 countries. This subanalysis included patients previously receiving long‐acting analogue insulin (AB; n = 348), or human basal insulin (long and intermediate acting) (HB; n = 3414), who were transferred to BIAsp 30. Efficacy end‐points included change in glycated haemoglobin (HbA_1c), fasting plasma glucose (FPG) and postprandial plasma glucose (PPG), from baseline to the end of the study. Episodes of hypoglycaemia, adverse events, and physician and patient satisfaction were also recorded. End‐points were considered separately by previous basal regimen (AB or HB). Results: After 6 months’ treatment with BIAsp 30, HbA_1c was significantly lowered in both groups (?1.60% and ?1.42% in the AB and HB groups; p < 0.0001 compared with baseline). Reductions in FPG and PPG were also statistically significant in both groups. The rate (events/patient/year) of overall hypoglycaemia remained relatively constant in patients switching from AB, but it was statistically lower in patients switching from HB (change from baseline ?3.8; p < 0.001). Conclusion: In routine clinical practice, patients with type 2 diabetes who are failing to reach glycaemic targets on basal insulin can achieve better glycaemic control without an increase in overall hypoglycaemia by intensifying with BIAsp 30.