Risk Factors For Diabetic Complications Research Articles

PDB94 - Evolution of the Market for oral Antidiabetic agents In Canada after Introduction of Dipeptidyl Peptidase-4 Inhibitors

Type 2 diabetes mellitus (DM) accounts for over 90% of all diagnosed diabetes cases. Hyperglycemia is an important risk factor for diabetic complications, supporting the use of glucose-lowering agents in the treatment of diabetes. Among glucose-lowering agents to treat type 2 DM are oral antidiabetic (OAD) agents. The objective of this study was to evaluate the Canadian market for OAD agents since 2008, soon after dipeptidyl peptidase (DPP)-4 inhibitors were introduced. Data on retail prescriptions and on drugstore and hospital purchases of OAD agents in Canada were obtained from IMS Brogan. Number of prescriptions and purchases (in $Can) were collected for 2008, 2012 and 2014. Total number of prescriptions for OAD agents in Canada amounted to 13.6 million, 20.5 million and 23 million in 2008, 2012, and 2014, respectively. Contribution of the two OAD agents mainly prescribed, metformin and sulfonylureas, decreased during this period while percentage of prescriptions for DPP-4 inhibitors over total OAD agents increased from 0.075% to 6.5% and to 14.5%, respectively, driven by the increase in prescriptions of sitagliptin, sitagliptin/metformin, saxagliptin, and linagliptin. Total drugstore and hospital purchases for OAD agents in Canada reached $394.2 million, $418.7 million and $520.9 million in 2008, 2012, and 2014, respectively. Percentage of purchases of DPP-4 inhibitors over total OAD agents markedly increased during this period, from 0.5% to 34.1% and to 64.1%, respectively. OAD agents represent a market of more than half a billion dollars in Canada; this will likely continue to grow due to the increasing occurrence of cases of type 2 DM in the general population. Since their introduction in 2008, DPP-4 inhibitor use has grown rapidly so that in 2014, they captured approximately one-sixth of prescriptions and, at almost two-thirds of purchases, were the market leaders among OAD agents.

Implementation of physiotherapeutic shares in the prevention of diabetes complications in a Family Health Strategy

Introduction In the Family Health Strategy (FHS), the treatment of Diabetes Mellitus (DM) includes education and lifestyle change strategies. Physiotherapists have a key role in this health setting. Objectives To implement actions of evaluation and guidelines for patients with type 2 DM who attend a Family Health Strategy (FHS), regarding diabetic foot and the practice of regular physical exercise in the control and prevention of the complications of Diabetes Mellitus. Methods 17 individuals from an FHS were evaluated, with the following procedures: clinical and anthropometric parameters, inspection, a questionnaire on diabetic neuropathy, tests of vibratory and tactile sensitivity, muscle function, range of motion, functional analysis, questions about exercise practice and guidance regarding controlling blood glucose and foot care. Results Deformities, dry skin, calluses, dehydration, ulceration, cracking and brittle nails were found. Peripheral neuropathy was not observed; tactile sensitivity was altered in the heel region and the vibratory sense was absent in 5% of individuals. A decrease in functionality of ankle movements was verified. Of the participants, 76% were sedentary, 24% knew about the benefits of practicing regular exercise, 25% had undergone a medical evaluation prior to performing physical exercise and, of these, 25% were supervised by a qualified professional. Discussion The implementation of physiotherapy actions in diabetics from an FHS was important for highlighting the presence of risk factors for diabetic complications. Conclusions Individuals attending the FHS need more information and programs for the prevention of diabetic complications.

Pharmacologic management of types 1 and 2 diabetes mellitus and their complications in women of childbearing age.

The numbers of women of childbearing age with pregestational diabetes mellitus (diabetes existing before pregnancy) are increasing, primarily because more patients are developing type 2 diabetes at younger ages. The teratogenicity associated with hyperglycemia in early pregnancy is well documented, and tight glucose control minimizes the risk of congenital malformation. Preconception planning is essential; thus contraception that does not worsen complications of diabetes is desirable. In addition, because contraceptives are not 100% effective, the treatment of elevated blood glucose levels, hypertension, and dyslipidemia in these women requires consideration of unplanned pregnancy. We summarized the literature to aid clinicians in choosing individualized treatment that minimizes risk in case pregnancy occurs and maximizes benefit in preventing the complications of diabetes. In women with well-controlled diabetes without vascular disease, all contraceptive methods are safe. Intrauterine devices are recommended due to their minimal effects on risk factors for diabetic complications and their lack of reliance on patient adherence for efficacy. Among insulins, the insulin analogs-insulin lispro, insulin aspart, and insulin detemir-offer patients greater convenience than regular insulin and NPH insulin, and they are safe in case of unplanned pregnancy. Of the noninsulin agents, glyburide and metformin are the safest during pregnancy, but many of the other agents pose minimal risk as long as they are withdrawn during early pregnancy. The risks and benefits of angiotensin-converting enzyme inhibitors in women with compelling indications must be weighed individually. In hypertensive patients at a high risk for unplanned pregnancy, nifedipine should be considered due to literature supporting its safety during early pregnancy. Pravastatin is recommended for women with dyslipidemia who are using effective contraception because there have been no reports of birth defects with this statin when used during early pregnancy in humans and animals.

Clinical Implications of Glucose Variability: Chronic Complications of Diabetes.

Glucose variability has been identified as a potential risk factor for diabetic complications; oxidative stress is widely regarded as the mechanism by which glycemic variability induces diabetic complications. However, there remains no generally accepted gold standard for assessing glucose variability. Representative indices for measuring intraday variability include calculation of the standard deviation along with the mean amplitude of glycemic excursions (MAGE). MAGE is used to measure major intraday excursions and is easily measured using continuous glucose monitoring systems. Despite a lack of randomized controlled trials, recent clinical data suggest that long-term glycemic variability, as determined by variability in hemoglobin A1c, may contribute to the development of microvascular complications. Intraday glycemic variability is also suggested to accelerate coronary artery disease in high-risk patients.

The relationship between glycemic variability and diabetic peripheral neuropathy in type 2 diabetes with well-controlled HbA1c.

BackgroundDiabetic peripheral neuropathy (DPN) is one of the most common microvascular complications of diabetes. Glycemic variability could be an independent risk factor for diabetes complications in addition to average glucose. Type 2 diabetes with well-controlled glycosylated hemoglobin A1c (HbA1c) may have different terms of glycemic variability and vascular complication consequences. The aim of the study is to investigate the relationship between glycemic variability and DPN in type 2 diabetes with well-controlled HbA1c (HbA1c < 7.0%).Methods45 type 2 diabetes with well-controlled HbA1c(HbA1c < 7.0%) and with DPN (DM/DPN group) were recruited in the study, and 45 type 2 diabetes with well-controlled HbA1c and without DPN (DM/–DPN group) were set as controls. The two groups were also matched for age and diabetic duration. Blood pressure, body mass index(BMI), insulin sensitivity index (Matsuda index, ISI), total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDLC), and low density lipoprotein cholesterol (LDLC) were tested in the two groups. And all patients were monitored using the continuous glucose monitoring (CGM) system for consecutive 72 hours. The multiple parameters of glycemic variability included the standard deviation of blood glucose (SDBG), mean of daily differences (MODD) and mean amplitude of glycemic excursions (MAGE).ResultsThe DM/DPN group had a greater SDBG, MODD and MAGE, when compared to the DM/–DPN group (p < 0.05). BMI, TC, and LDLC of DM/DPN group were lower than those of DM/–DPN group (p < 0.05). The patients with hypoglycemia were comparable between the two groups (p > 0.05). Univariate analysis showed DPN was closely associated with BMI (OR 0.82, CI 0.72–0.94, p = 0.005), TC (OR 0.63, CI 0.42–0.93, p = 0.02), LDLC (OR 0.4, CI 0.20–0.80, p = 0.009), SDBG (OR 2.95, CI 1.55–5.61, p = 0.001), MODD (OR 4.38, CI 1.48–12.93, p = 0.008), MAGE (OR 2.18, CI 1.47–3.24, p < 0.001). Multivariate logistic regression analysis showed that MAGE (OR 2.05, CI 1.36–3.09, p = 0.001) and BMI (OR 0.85, CI 0.73–0.99, p = 0.033) were significantly correlating with DPN. Glycemic variability, evaluated by MAGE, was the most significantly independent risk factor for DPN.ConclusionsThere was a close relationship between glycemic variability evaluated by MAGE and DPN in type 2 diabetes with well-controlled HbA1c.

L-cysteine is a potent inhibitor of protein glycation on both albumin and LDL, and prevents the diabetic complications in diabetic–atherosclerotic rat

The aim of the present study is to investigate the protective effect of l-cysteine (Cys) on protein glycation, and hence, the improvement of diabetic complications. Streptozotocin-induced diabetic rats on an atherogenic diet were used as a model. Two groups of rats, normal and diabetic, were treated with 0.05% of Cys in drinking water for 3months and two others received water only. Some parameters including: glucose, insulin, glycation products, activity of the glyoxalase system, lipid profile, oxidation markers, high sensitivity CRP (Hs CRP) and creatinine in the serum, and protein in the urine of all rats were determined. Furthermore, rat serum albumin and LDL were purified and incubated with glucose in the presence and absence of Cys and the samples were investigated for glycation and oxidation products. Cys showed an inhibitory effect on glycation and oxidation products in both in vivo and in vitro conditions. It reduced glucose, insulin resistance, triglyceride, cholesterol, LDL, Hs CRP and creatinine in the serum; and the proteinuria; furthermore, it increased HDL and glyoxalase system activity in the serum of the diabetic–atherosclerotic rats. Cys reduced all of the risk factors of diabetic complications and showed anti-atherosclerotic potential; thus it is useful in diabetes treatment.

A Retrospective Study in 5,989 Patients with Type 1 Diabetes in 10 Outpatient Diabetes Clinics in Sweden of the Frequency of Measuring HbA1c in Clinical Practice

Aim: Guidelines for the treatment of type 1 diabetes generally recommend quarterly or more frequent Haemoglobin A1c (HbA1c) assessment in patients with inadequate glycaemic control. The purpose of the current study was to evaluate to what extent these guidelines are followed in clinical practice in Sweden. Method: We studied 5989 patients with type 1 diabetes from 10 outpatient diabetes clinics in Sweden from 1 January 2005 to 31 December 2009. Data on HbA1c measurement frequency were obtained from the Diab-Base electronic medical records database, where HbA1c measurements are recorded together with other patient characteristics, including treatment and other general risk factors for diabetic complications. The frequency of HbA1c measurements was obtained for all patients by calendar year, care unit, and during time periods where glucose was classified as well controlled (HbA1c<=7.0%) or inadequate (HbA1c 7.0% or higher). Results: The mean annual number of HbA1c assessments when glucose control was inadequate was 1.83 compared with 1.58 during well controlled time-periods. In 35.4% of cases the next HbA1c check following an HbA1c >7% was performed within 4 months. The probability of a subsequent assessment in the 4 months following an HbA1c value>7.0% increase in patients treated with continuous subcutaneous insulin infusion (CSII), OR=1.57 (1.46-1.69). Differences were also noted by care unit, age, gender, glycaemic control, calendar year, and weight and diabetes duration. Conclusion: In patients with type 1 diabetes, HbA1c is measured less frequently in clinical practice in Sweden than guidelines recommend, although patients with CSII and treated in certain care units receive more frequent assessments.

Effect of single oral dose of proanthocyanidin on postprandial hyperglycemia in healthy rats: A comparative study with sitagliptin.

Background:Many of flavonoid rich natural products found to have a significant influence on postprandial hyperglycemia, a major risk factor for diabetic complications. Enhancement of insulinotropic gut hormones by inhibition of dipeptidyl peptidase-IV (DPP-IV) are among the newest strategies for treatments of Type 2 diabetes which thought to be the underlying action through which flavonoid can reduce postprandial hyperglycemia.Aim:This study aim was designed to investigate the potential role of standardized grape seed proanthocyanidin in controlling postprandial hyperglycemia by enhancing the regulatory incretin effect of gut hormones in response to oral and intraperitoneal (I.P) glucose load in healthy rats.Materials and Methods:Five groups of animals each of six rats were used in this study, which was conducted in March 2013. Groups (II and V) treated with single oral dose of proanthocyanidin (50 mg/kg), Group III received single oral dose of sitagliptin (40 mg/kg) and Groups (I and IV) treated with vehicle serve as control groups. All treatments were given 30 min before oral or I.P glucose load. Blood glucose was estimated over 2 h duration at (0, 30, 60, 90, and 120) min from glucose load.Result:Both proanthocyanidin and sitagliptin significantly improve hyperglycemia induced by oral glucose load relative to control. While non-significant changes were achieved by proanthocyanidin after I.P glucose challenge compared to untreated control group.Conclusion:The result of this study indicated that proanthocyanidin may possess an enhancement of incretin effect of gut peptides, which could be responsible for some of its action on glucose homeostasis. This finding may provide an opportunity for further pharmacological studies using more specific models to clarify the possible action of proanthocyanidin as a natural DPP-IV inhibitor.

Glycated hemoglobin variability and retinopathy progression in type1 diabetes: Is month-to-moth instability a better predictor?

Glucose instability has been proposed to be one of the risk factors for diabetic complications, in particular retinopathy, since the publication of the Diabetes Control and Complication Trial (DCCT) 20 years ago. In that study, as compared with conventional therapy, intensive therapy effectively delays the onset and slows the progression of diabetic complications in patients with type 1 diabetes1. The following analyses have found that in addition to mean glycated hemoglobin (HbA1c) level, high HbA1c variability, but not glucose variability, might be associated with increased risks of retinopathy, nephropathy and perhaps neuropathy, in type 1 diabetic patients (Table 1)2-8. Although many laboratory and clinical studies suggested that ‘short-term’ glucose fluctuation, mostly driven by high postprandial blood glucose levels, leading to increased oxidative stress and decreased endothelial function, is responsible for the higher risks of microvascular and cardiovascular outcomes in type 2 diabetic patients9, the role of ‘longer-term’ glucose stability in terms of HbA1c variability, and the occurrence and progression of diabetic complications among type 1 diabetic patients remains elusive. Retinopathy Nephropathy Retinopathy Nephropathy Retinopathy Nephropathy Neuropathy DCCT EDIC (first 4 years) Retinopathy Nephropathy ORPS NFS In a recently published study, Hietala et al.10 analyzed data from 2,019 type 1 diabetic patients who were enrolled in the Finnish Diabetic Nephropathy (FinnDiane) study. During the average follow up of 5.2 years, they have reconfirmed that high HbA1c variability was associated with an increased risk of incidence, as well as laser treatment for retinopathy. In the earlier report, they also showed that HbA1c variability was not only predictive of incident microalbuminuria and progression of renal disease, but also of incident cardiovascular events in type 1 diabetic patients7. Of note, patients with high mean HbA1c values also had high HbA1c variability. However, patients with low mean HbA1c value, but high HbA1c variability, had similar incidence for nephropathy progression as patients with high mean HbA1c value, but low HbA1c variability, suggesting an equally important effect of both absolute value and stability in the risk of progression in renal outcome. The significant association between HbA1c variability, and risks of retinopathy and nephropathy persisted even after taking the number of HbA1c measurements into consideration. Why was HbA1c instability independently associated with a higher chance of laser treatment for retinopathy? The authors emphasized that even short periods of higher HbA1c could have a sustained effect on worsening of retinopathy despite subsequent improvement in glycemic control10. However, because of the inherent limitations in the observational study design, there might be other explanations for the observed association (Figure 1). First, because there might be a lag time between worsening of visual symptoms and laser treatment, it is possible that diagnosis of retinopathy progression per se leads to attempts to improve glycemic control by physicians, and hence increasing HbA1c fluctuation (protopathic bias or reverse causation). Second, for poorly controlled patients with high and unstable HbA1c value, physicians were more likely to do fundoscopic or fundus photographic examinations, and were hence more likely to find retinopathy progression that might require laser treatment (detection bias). Third, from prior studies we knew that a variable HbA1c profile is associated with several factors, such as low socioeconomic status, physical inactivity and smoking7. Perhaps, it is these lifestyle and behavior factors (including medication non-adherence) that lead to poor outcomes. Again, we want to reassure our patients that long-term optimal glycemic control is crucial to reduce retinopathy occurrence and its complications. For healthcare professionals who are involved in the care of diabetic patients, the findings of the study by Hietala et al.10 highlight that patients with highly variable HbA1c warrant careful monitoring of retinopathy development and progression. Further research on the mechanism of the observed association and how to prevent early retinopathy worsening for those poorly controlled type 1 patients undergoing intensive glucose lowering therapy are required to fill the knowledge gap.

Glycemic variability in relation to oral disposition index in the subjects with different stages of glucose tolerance

BackgroundGlucose variability could be an independent risk factor for diabetes complications in addition to average glucose. The deficiency in islet β cell secretion and insulin sensitivity, the two important pathophysiological mechanisms of diabetes, are responsible for glycemic disorders. The oral disposition index evaluated by product of insulin secretion and sensitivity is a useful marker of islet β cell function. The aim of the study is to investigate glycemic variability in relation to oral disposition index in the subjects across a range of glucose tolerance from the normal to overt type 2 diabetes.Methods75-g oral glucose tolerance test (OGTT) was performed in total 220 subjects: 47 with normal glucose regulation (NGR), 52 with impaired glucose metabolism (IGM, 8 with isolated impaired fasting glucose [IFG], 18 with isolated impaired glucose tolerance [IGT] and 26 with combined IFG and IGT), 61 screen-diagnosed diabetes by isolated 2-h glucose (DM2h) and 60 newly diagnosed diabetes by both fasting and 2-h glucose (DM). Insulin sensitivity index (Matsuda index, ISI), insulin secretion index (ΔI30/ΔG30), and integrated β cell function measured by the oral disposition index (ΔI30/ΔG30 multiplied by the ISI) were derived from OGTT. All subjects were monitored using the continuous glucose monitoring system for consecutive 72 hours. The multiple parameters of glycemic variability included the standard deviation of blood glucose (SD), mean of blood glucose (MBG), high blood glucose index (HBGI), continuous overlapping net glycemic action calculated every 1 h (CONGA1), mean of daily differences (MODD) and mean amplitude of glycemic excursions (MAGE).ResultsFrom the NGR to IGM to DM2h to DM group, the respective values of SD (mean ± SD) (0.9 ± 0.3, 1.5 ± 0.5, 1.9 ± 0.6 and 2.2 ± 0.6 mmol/), MBG (5.9 ± 0.5, 6.7 ± 0.7, 7.7 ± 1.0 and 8.7 ± 1.5 mmol/L), HGBI [median(Q1–Q3)][0.8(0.2–1.2), 2.0(1.2–3.7), 3.8(2.4–5.6) and 6.4(3.2–9.5)], CONGA1 (1.0 ± 0.2, 1.3 ± 0.2, 1.5 ± 0.3 and 1.8 ± 0.4 mmol/L), MODD (0.9 ± 0.3, 1.4 ± 0.4, 1.8 ± 0.7 and 2.1 ± 0.7 mmol/L) and MAGE (2.1 ± 0.6, 3.3 ± 1.0, 4.3 ± 1.4 and 4.8 ± 1.6 mmol/L) were all increased progressively (all p < 0.05), while their oral disposition indices [745(546–947), 362(271–475), 203(134–274) and 91(70–139)] were decreased progressively (p < 0.05). In addition, SD, MBG, HGBI, CONGA1, MODD and MAGE were all negatively associated with the oral disposition index in each group (all p < 0.05) and in the entire data set (r = −0.66, –0.66, –0.72, –0.59, –0.61 and −0.65, respectively, p < 0.05).ConclusionsIncreased glycemic variability parameters are consistently associated with decreased oral disposition index in subjects across the range of glucose tolerance from the NGR to IGM to DM2h to DM group.

Clinical and Technical Factors Associated with Skin Intrinsic Fluorescence in Subjects with Type 1 Diabetes from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study

The Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications(EDIC) studies have established multiyear mean hemoglobin A1c (HbA1c) as predictive of microvascular complications in persons with type 1 diabetes. However, multiyear mean HbA1c is not always available in the clinical setting. Skin advanced glycation end products (AGEs) are thought to partially reflect effects of hyperglycemia over time, and measurement of skin AGEs might be a surrogate for multiyear mean HbA1c. As certain AGEs fluoresce and skin fluorescence has been demonstrated to correlate with the concentration of skin AGEs, noninvasive measurement by skin intrinsic fluorescence(SIF) facilitates the exploration of the association of mean HbA1c and other clinical/technical factors with SIF using the detailed phenotypic database available in DCCT/EDIC. Of the subjects, 1,185 (53% male) had measurements of SIF during years 16/17 of EDIC with mean age and diabetes duration of 51.5 and 29.8 years, respectively. SIF measurements were obtained on the underside of the forearm near the elbow using a skin fluorescence spectrometer. Demographic data and health history were self-reported, and an annual standardized examination measured clinical status. Linear regression models were constructed to identify significant clinical and technical factors associated with SIF, and the final models only used factors that were significant. SIF ranged from 8.7 to 54.0 arbitrary units and was log-normally distributed. Log(SIF) correlated more with mean HbA1c as the time period increased. In multivariate analyses log(SIF) was significantly associated with mean HbA1c, age,estimated glomerular filtration rate < 60mL/min/m2, smoking status, skin tone, and clinic latitude <37 N. SIF reflects age, mean HbA1c over time, smoking, and renal damage, which are known risk factors for diabetes complications.

Nateglinide and Acarbose Are Comparably Effective Reducers of Postprandial Glycemic Excursions in Chinese Antihyperglycemic Agent–Naive Subjects with Type 2 Diabetes

Recent studies have identified postprandial glycemic excursions as risk factors for diabetes complications. This study aimed to compare the effects of nateglinide and acarbose treatments on postprandial glycemic excursions in Chinese subjects with type 2 diabetes. This was a multicenter, open-label, randomized, active-controlled, parallel-group study. One hundred three antihyperglycemic agent-naive subjects with type 2 diabetes (hemoglobin A1c range, 6.5-9.0%) were prospectively recruited from four hospitals in China. The intervention was nateglinide (120 mg three times a day) or acarbose (50 mg three times a day) therapy for 2 weeks. A continuous glucose monitoring system was used to calculate the incremental area under the curve of postprandial blood glucose (AUCpp), the incremental glucose peak (IGP), mean amplitude of glycemic excursions, SD of blood glucose, the mean of daily differences, and 24-h mean blood glucose (MBG). Subjects' serum glycated albumin and the plasma insulin levels were also analyzed. Both agents caused significant reductions on AUCpp and IGP. Similarly, both treatment groups showed significant improvements in the intra- and interday glycemic excursions, as well as the 24-h MBG and serum glycated albumin compared with baseline (P<0.001). However, neither of the agents produced a significantly better effect (P>0.05). Moreover, the nateglinide-treated group had significantly increased insulin levels at 30 min and at 120 min after a standard meal compared with baseline, whereas the acarbose-treated group decreased. No serious adverse events occurred in either group. The rates of hypoglycemic episodes were comparable in the two groups, and no severe hypoglycemic episode occurred in either group. Nateglinide and acarbose were comparably effective in reducing postprandial glycemic excursions in antihyperglycemic agent-naive Chinese patients with type 2 diabetes, possibly through different pathophysiological mechanisms.

Pharmaceutical consultation as a tool to improve health outcomes for patients with type 2 diabetes

This study develops and evaluates a pharmaceutical consultation program (PCP) to improve treatment for Type 2 diabetes patients (T2DP) and reduce risk factors for diabetic complications with possible application in other chronic diseases. We recruited T2DP receiving conventional medical treatment but with fasting glycemia &gt;140mg/dl and/or glycated hemoglobin &gt;7%. The PCP includes strategies obtained from Dader's method, the PWDT (Pharmacist's Workup of Drug Therapy method) model of pharmaceutical care, the SOAP (Subjective data, Objective data, Assessment, and Plan of care) method, and concepts based on a nursing care model. The PCP evaluated lifestyle, pharmacotherapy and monitoring it using laboratory tests, vital signs, and anthropometry. These procedures were repeated every 4 months for 1 year. Data obtained in each consultation were used to provide patient education focusing on healthy lifestyles and medications. Fifty patients completed the PCP. There were reductions in glycemia (P&lt;0.0001), glycated hemoglobin (P=0.0022), cholesterolemia (P=0.0072), triacylglycerolemia (P=0.0204) and blood pressure (P&lt;0.0001). Increased concordance with drug treatment and correction of drug-related problems contributed to improved treatment. We can therefore conclude that our PCP was suitable for improving health outcomes in T2DP by reducing risk factors for diabetic complications.

Association between Haptoglobin Genotype Polymorphism and Type Two (2) Diabetes in Accra, Ghana

Polymorphism of the haptoglobin (Hp) gene, characterized by alleles Hp1 and Hp2, gives rise to structurally and functionally distinct Hp protein phenotypes: Hp1-1, Hp2-1, and Hp2-2. The corresponding proteins have structural and functional differences that have influence on a particular disease. For example, Hp genotype is an independent risk factor for diabetic complications. In urban Ghana, type two diabetes mellitus (T2DM) affects at least 6% of adults. The aim of this study was to assess the association between Hp genotype polymorphism in T2DM patients in Accra. The study was a case control one. A total of 100 participants, 50 T2DM patients attending the Diabetes Clinic (Korle-Bu Teaching Hospital) and 50 healthy non-diabetic controls, were involved. Plasma glucose concentration was measured by the glucose-oxidase method. Fasting blood glucose was performed on all subjects except for the individuals with a history of T2DM. Hp genotype was determined by allele specific polymerase chain reaction (PCR). PCR produced Hp genotype-specific bands for the Hp1F, Hp1S, and Hp2 alleles. Statistical analyses revealed a significant difference in the Hp genotype distribution between diabetics and non-diabetics (2 = 7.84, df = 2, p = 0.0198). Hp1-1 was the most frequent genotype among non-diabetics (58%) whilst Hp2-2 (38%) was most frequent genotype among diabetics. Majority of the diabetics were found in the Hp1S-1F and Hp2-2 genotype groups for diastolic BP (mmHg), systolic BP (mmHg) and FBG (mM). There was a strong association between DM and Hp2-2 genotype, followed by Hp2-1 (Hp1F-2 > Hp1S- 2) with the least being Hp1-1 (Hp1F-1F, Hp1S-1F, Hp1S-1S). The risk of developing diabetes among people with Hp2-2 and Hp1F-2 genotypes was high. They can therefore be used as markers for an individual developing DM.

Combined Exercise Training and Self-Management Education for Community-Dwelling Older Adults with Diabetes in Korea

This study examined the effect of a combined program of exercise training and self-management education on risk factors for diabetes complications and adherence behavior. A two-group, quasi-experimental study design was used to test the 12-week intervention program with community-dwelling older adults in Korea. Change scores (from baseline to Week 13) of outcome variables were compared between the intervention group (n = 21) and the control group (n = 16). The change scores in triglyceride levels, body weight, body mass index, and diabetes self-management behavior showed significant differences between groups. However, no significant differences were found in A1C and blood pressure change scores between the groups in this sample, in which these characteristics were relatively well controlled at baseline. The results of this study showed some promising synergistic effects of lowering cardiovascular risk factors from combining the two interventions.

The Relationship between Glucose Excursion and Cognitive Function in Aged Type 2 Diabetes Patients

ObjectiveEvidence suggests that type 2 diabetes (T2DM) is associated with an increased risk of dementia and that glucose variability is an independent risk factor for diabetic complications. This study investigated the relationship between glucose excursion and cognitive function in aged T2DM patients. MethodsA total of 248 aged T2DM patients wore a continuous glucose monitoring system (CGMS) for 3 days in order to evaluate glucose excursion, including mean amplitude of glycemic excursions (MAGE) and mean of daily difference (MODD). All subjects were evaluated with a number of accepted cognitive function tests, including the mini-mental status examination (MMSE). The relationship between MAGE and MODD and performance on these cognitive tests was assessed. ResultsThe MAGE and MMSE score were negatively correlated, likewise with the correlation between MODD and MMSE. Liner multivariate regression analysis showed that MAGE and MODD were also negatively related to MMSE independent of age, sex, glycemic control, hypertension, smoking, or coronary heart disease history. ConclusionGlucose excursion is related to cognitive function in aged T2DM patients. Elevated glucose excursion decreased the MMSE score, which reflects general cognitive function. Thus, therapy aimed at controlling glucose excursion may be beneficial for maintaining cognitive function in aged T2DM patients.

Effect of quercetin on postprandial glucose excursion after mono- and disaccharides challenge in normal and diabetic rats

Postprandial hyperglycemia is a major risk factor for diabetic complications leading to disabilities and mortality in diabetics. Quercetin, a flavonoid, has been tried in traditional medicine for treating diabetes. The present study was designed to evaluate the potential of quercetin to control postprandial blood glucose level after maltose and glucose loading in normal and STZ-induced diabetic rats. Normal male Albino wistar rats and STZ-induced diabetic rats were treated with 300 and 600 mg/kg quercetin orally to evaluate the effect on postprandial hyperglycemia after carbohydrate loading, using acarbose as comparator. The results clearly showed ameliorated postprandial hyperglycemia due to the use of quercetin (300 and 600 mg/kg), it significantly dampened the postprandial hyperglycemia by 32.0% and 64.0% respectively, in maltose loaded diabetic rats, and 30.3% after 300 mg/kg dose in normal rats, compared to control; while acarbose produced 51% and 54% decrease in this respect in the two models respecttively. Quercetin in 600 mg/kg dose produces significantly more reduction in postprandial hyperglycemia compared to acarbose, while in rats that received glucose and quercetin, postprandial hyperglycemia was not significantly affected. In conclusion, quercetin effectively suppresses postprandial hyperglycemia in STZ-induced diabetic rats loaded with maltose, which may be attributed to α-glucosidase inhibition. Quercetin could be used as a potential supplement for treating postprandial hyperglycemia.

Role of Protein Kinase C-MAPK, Oxidative Stress and Inflammation Pathways in Diabetic Nephropathy

Diabetic nephropathy is the most common cause of end-stage renal disease. It is assumed that hyperglycemia is one of the major systemic risk factors for diabetic complications. Numerous hypotheses exist to enlighten the adverse effect of hyperglycemia. One of these hypotheses is the activation of the calcium- and phospholipid-dependent protein kinase C signaling pathway by hyperglycemia which subsequently mediates cellular response and affects gene expression and protein function to cause cellular dysfunction and damage. It is well known that the intracellular protein kinase C activation is achieved by the elevated diacylglycerol levels in vascular tissues as well as in nonvascular tissues. Besides diacylglycerol, oxidative stress has also been reported to induce prolonged activation of protein kinase C within cells through the reactive oxygen species. Activation of protein kinase C and oxidative stress have been associated with vascular alterations such as increases in permeability of endothelial cells, extracellular matrix synthesis, cell growth and apoptosis, angiogenesis, and cytokines activation and inhibition. These derangements in vascular cell homeostasis caused by the activation protein kinase C as well as oxidative stress are connected to the occurrence of pathologies affecting large vessel and small vessel complications. Accumulating evidences have also shown that the inflammation process is an essential pathogenetic mechanism in diabetic nephropathy. Therefore, modulation of this process is an important target for both metabolic and hemodynamic derangements in diabetic nephropathy. In this review, we will discusses the role of protein kinase C, oxidative stress and inflammation process and the signaling pathway in the pathogenesis of diabetic nephropathy.

Reduced muscle carnosine content in type 2, but not in type 1 diabetic patients

Carnosine is present in high concentrations in skeletal muscle where it contributes to acid buffering and functions also as a natural protector against oxidative and carbonyl stress. Animal studies have shown an anti-diabetic effect of carnosine supplementation. High carnosinase activity, the carnosine degrading enzyme in serum, is a risk factor for diabetic complications in humans. The aim of the present study was to compare the muscle carnosine concentration in diabetic subjects to the level in non-diabetics. Type 1 and 2 diabetic patients and matched healthy controls (total n=58) were included in the study. Muscle carnosine content was evaluated by proton magnetic resonance spectroscopy (3 Tesla) in soleus and gastrocnemius. Significantly lower carnosine content (-45%) in gastrocnemius muscle, but not in soleus, was shown in type 2 diabetic patients compared with controls. No differences were observed in type 1 diabetic patients. Type II diabetic patients display a reduced muscular carnosine content. A reduction in muscle carnosine concentration may be partially associated with defective mechanisms against oxidative, glycative and carbonyl stress in muscle.

Post-prandial glucose and diabetic complications: systematic review of observational studies

Post-prandial hyperglycemia is considered a relevant therapeutic target in type 2 diabetic patients, and it could represent per se an independent risk factor for diabetic complications. Aim of the present systematic review is to collect and summarize evidence from observational studies on the relationship between post-prandial glucose (PPG) and cardiovascular or microvascular disease in patients with diabetes. An extensive search of Medline (any date up to December 31, 2010) was performed for all longitudinal epidemiological studies with a cohort design. The following endpoints were taken into consideration: death from any cause; cardiovascular death and micro- and macrovascular complications. The number of epidemiological studies assessing the relationship between PPG and microvascular or cardiovascular disease in subjects with diabetes is surprisingly scarce. In fact, of the 391 retrieved studies, only 8 fulfilled the inclusion criteria. Most of those investigations enrolled small samples, which in many instances were not representative of the general population. Furthermore, the assessment of PPG varied widely across studies. These considerations prevent any formal meta-analysis. Despite this, the few available studies show that higher PPG is associated with increased all-cause and cardiovascular death, incidence of major cardiovascular events (including myocardial infarction and stroke), and progression of diabetic retinopathy.