Rajesh Peter

Can Admission and Fasting Glucose reliably identify Undiagnosed Diabetes in Patients with Acute Coronary Syndrome

OBJECTIVE—Our objectives were to determine the prevalence of previously undiagnosed abnormal glucose tolerance, i.e., diabetes and impaired glucose tolerance (IGT) in patients with acute coronary syndrome and to assess the utility of admission and fasting glucose in identifying diabetes in these patients. RESEARCH DESIGN AND METHODS—Glycemic status was characterized on the basis of admission plasma glucose (APG), fasting plasma glucose (FPG), and an oral glucose tolerance test (OGTT) in 140 patients admitted to the hospital with acute coronary syndrome, who were not known to have diabetes (mean ± SD age 67.3 ± 13.4 years; 79% men). OGTTs were performed on days 5–7 after admission. RESULTS—The prevalences of diabetes and IGT were 27 and 39%, respectively, according to OGTT criteria. Receiver operating characteristic curves showed that the area under the curve for diagnosing diabetes was 0.83 (P < 0.001) for FPG, 0.79 (P < 0.001) for APG, and 0.84 (P < 0.001) for FPG and APG applied in combination. A FPG cutoff ≥5.6 mmol/l (100 mg/dl) and/or APG ≥7.8 mmol/l (140 mg/dl) yielded a sensitivity of 89.5% and a positive predictive value of 43.6% for detecting diabetes. CONCLUSIONS—A high prevalence of abnormal glucose tolerance was seen in patients with acute coronary syndrome. The combination of FPG ≥5.6 mmol/l (100 mg/dl) and/or APG ≥7.8 mmol/l (140 mg/dl) was highly sensitive for identifying diabetes. Although weakly specific, this simple algorithm could offer a practical initial screening tool at the acute setting in the high-risk population with acute coronary syndrome.

Relative and absolute contributions of postprandial and fasting plasma glucose to daytime hyperglycaemia and HbA1cin subjects with Type-2 diabetes

Aims  To determine the relative and absolute contributions of postprandial glucose (PPG) and fasting or preprandial plasma glucose (FPG) to daytime hyperglycaemia and HbA1c respectively, in persons with type 2 diabetes (T2DM).

A comparison of preprandial insulin glulisine versus insulin lispro in people with Type 2 diabetes over a 12-h period

A comparison of the plasma glucose and insulin day profiles between two prandial rapid-acting insulin analogues, insulin glulisine (glulisine) and insulin lispro (lispro), in 18 obese subjects with Type 2 diabetes. Subjects (body mass index: males, 36.7 [33.2-43.8] kg/m(2); females, 40.0 [35.7-46.5] kg/m(2)) received subcutaneous glulisine or lispro (0.15 U/kg) at 4-h intervals immediately (within 2 min) before three standard test meals during each of two 12-h, randomised, open-label, crossover studies (7+/-2-day interval between each). Overall, preprandial-subtracted glucose concentrations (area under the curve) were similar on the glulisine and lispro study days. However, the mean of the three maximal preprandial subtracted plasma glucose concentrations (DeltaGLU(max)) were lower with glulisine versus lispro (12%; p<0.01). Mean concentrations of insulin analogue were significantly higher post-meal with glulisine (p<0.01 for all). Post hoc analysis showed a significantly faster absorption rate for glulisine versus lispro in the first 30 min post-meal (estimated difference 0.48 microU/min; p<0.0001). Only two cases of hypoglycaemia were reported; both from one subject during the lispro day. When glulisine is injected immediately before a meal in obese patients with Type 2 diabetes, glulisine achieves significantly lower glucose excursions over lispro. Significantly faster absorption with higher and sustained post-meal levels of insulin analogue was achieved at every meal with glulisine versus lispro.

Relationship between HbA1c and indices of glucose tolerance derived from a standardized meal test in newly diagnosed treatment naive subjects with Type 2 diabetes

Aims  To determine the relationship between HbA1c and other indices of glycaemic status derived during a standardized meal tolerance test (MTT) in newly diagnosed treatment‐naive subjects with Type 2 diabetes (T2DM).

Daytime variability of postprandial glucose tolerance and pancreatic B-cell function using 12-h profiles in persons with Type 2 diabetes.

Diabet. Med. 27, 266–273 (2010)

Review: Postprandial glycaemia and cardiovascular risk

Cardiovascular disease (CVD) accounts for almost 75% of mortality in subjects with type 2 diabetes. There is emerging evidence (epidemiological and There is emerging evidence (epidemiological and experimental studies) that postprandial glucose (PPG) contributes significantly to CVD risk, although to date there are no large scale interventional studies with the primary objective of reducing cardiovascular complications by targeting PPG. There is still continuing debate about the definition of postprandial hyperglycaemia. Moreover, we now know more of the cellular mechanisms being triggered in response to glucose excursions which may offer an explanation to this increased susceptibility to CVD. The contribution of PPG to glycosylated haemoglobin, is predominant in relatively well controlled subjects with type 2 diabetes. Hence, PPG is emerging as a legitimate therapeutic target to minimise CVD risk.This review looks at the evidence linking postprandial hyperglycaemia to CVD, the cellular mechanisms explaini...

Diabetes: coronary heart disease equivalent?

DOI:10.1097/MOL.0b013e32834f42c6 It has been known for some time that diabetes mellitus is associated with increased risk of cardiovascular disease. The term coronary heart disease (CHD) risk equivalence has attracted much controversy since the publication of the study by Haffner et al. [1]. A number of interventional strategies based on this assumption have been put into place to reduce CHD risk by various societies as the number of people with diabetes increases. However, it must be questioned if this risk exists in all patients with diabetes, especially those who have been newly diagnosed or those with a relatively short duration of the condition or even patients with no other risk factors. There are also studies indicating that diabetes does not confer the same risk for a future cardiovascular event compared to a patient who already has CHD [2]. This blanket risk approach has resource implications, and also some of the treatments used to decrease this risk can have potentially serious side-effects. A recent study assessed the impact of age at onset and duration of diabetes on CHD risk [3 && ]. Men with diabetes diagnosed at the age of at least 60 years (mean diabetes duration 4.9 years) had a CHD risk approximately half that in patients who developed diabetes before the age of 60 years (mean diabetes duration 16.7 years). Although both late and early onset diabetes were associated with significantly increased cardiovascular event risk even after adjustment for other risk factors, CHD risk equivalence was only observed in the latter group of diabetic patients with a longer duration of the condition. Hence, patients with diabetes will have the condition for a few years before the risk for a cardiovascular event reaches the level equivalent for a patient with previous CHD. In subgroup analysis, the authors indicate that CHD risk escalates significantly with disease duration and approaches CHD risk equivalence only when the disease duration is beyond 8 years. This pattern of increasing risk with time emphasizes the need to be aggressive with CHD risk reduction in patients with type 2 diabetes diagnosed at a relatively young age and increased duration of the condition. It also indicates that prudence must be observed in pursuing aggressive risk reduction strategies in newly diagnosed patients with diabetes

Insulin therapy in type 2 diabetes: insulin analogue mix 50, a potential role in reducing postprandial hyperglycaemia and cardiovascular disease

Importance of the field: Postprandial hyperglycaemia is becoming topical, with studies suggesting a link to cardiovascular disease. Recently, a number of new therapies for the treatment of type 2 diabetes have become available. Areas covered in this review: This review looks at the evidence for the potential role of insulin analogue mix 50 to reduce postprandial hyperglycaemia and cardiovascular disease. Search Strategy: Medline and Embase databases were searched using the MeSH terms to identify relevant studies from 1980 to 2009. Both original articles and reviews were extracted. Published reference lists were also examined. MeSH terms used for literature searching: human insulins, insulin analogues, insulin analogue mix 50, glycaemia, postprandial glucose, fasting glucose, type 2 diabetes, type 1 diabetes, cardiovascular disease. What the reader will gain: The reader is presented with evidence discussing the importance of postprandial hyperglycaemia and studies comparing different insulin regimes and in particular insulin analogue mix 50 and its potential to reduce postprandial glucose surges and reduce cardiovascular disease. Take-home message: Insulin analogue mix 50 is a viable therapeutic option in a sub-group of patients with type 2 diabetes.

DIABETIC RETINOPATHY IN NEWLY DIAGNOSED SUBJECTS WITH TYPE 2 DIABETES MELLITUS : CONTRIBUTION OF β-CELL FUNCTION

PURPOSE The association of hyperglycemia and diabetic retinopathy (DR) in established type 2 diabetes mellitus (T2DM) subjects is well accepted. However, the association between β-cell responsiveness and insulin sensitivity leading to fasting and postprandial hyperglycemia with DR in newly diagnosed treatment-naïve T2DM subjects remain unreported. METHODS A total of 544 newly diagnosed treatment-naïve T2DM subjects were screened for DR (digital photography) and underwent a standardized meal tolerance test. Serial plasma glucose and insulin levels were measured, and fasting (M0) and postprandial β-cell responsiveness calculated Calculating Pancreatic Response Program along with homeostasis model assessment-β cell function (HOMA-B) and HOMA-Insulin Sensitivity. A subgroup of 201 subjects also underwent a frequently sampled IV glucose tolerance test and the acute insulin response to glucose, insulin sensitivity, and glucose effectiveness (SG) estimated (MINMOD model). RESULTS A total of 16.5% (90) subjects had DR at diagnosis. Subjects with DR had significantly reduced M0, HOMA-B and SG leading to higher fasting and postprandial (2 hour) glucose and significantly lower fasting and postprandial (2 hour) insulin. Factors independently associated with DR in multivariate logistic regression analysis were M0, HOMA-B, and SG with fasting and postprandial (2 hour) glucose and insulin. There was no statistical difference in glycated hemoglobin, systolic blood pressure, acute insulin response to glucose, and insulin sensitivity between those with or without DR. PRINCIPAL CONCLUSIONS In this cohort of newly diagnosed T2DM subjects, DR is associated with reduced β-cell responsiveness, resulting from β-cell failure rather than insulin resistance, leading to fasting and postprandial hyperglycemia and hypoinsulinemia.

Hyperlipidaemia and cardiovascular disease -- newer antihyperglycaemic agents and cardiovascular disease.

DOI:10.1097/MOL.0b013e32835ec5f5 Type 2 diabetes mellitus (T2DM) is associated with increased risk of cardiovascular disease (CVD). It has also become apparent that age of onset and duration of diabetes are important factors that influence this increased risk [1]. Addressing cardiovascular risk by means of tight glycaemic control in all patients with T2DM may be counterproductive as was demonstrated by the action to control cardiovascular risk in diabetes (ACCORD) study [2]. There were various factors hypothesized that could have resulted in this unexpected finding including hypoglycaemia, weight gain and fluid retention. As a result, antihyperglycaemic medications that avoid these complications seem logical to use in this setting. A number of new medications have recently been introduced to treat T2DM. Dapagliflozin, a sodium glucose transporter 2 (SGLT2) inhibitor, the first in this new class of drugs has just been licensed. Various other drugs in this class are in phase II/III stages of development. These compounds act by selectively inhibiting the high capacity, low-affinity SGLT2 receptors in the proximal tubule of the kidney increasing urinary glucose excretion and reducing hyperglycaemia. Studies have demonstrated that in addition to reducing hyperglycaemia, patients experienced weight loss (possibly because of both early osmotic diuretic effect and calorie loss) [3 && ], reductions in waist circumference [4], systolic blood pressure [5] and mild increases in HDL and decrease in triglycerides [5]. All these properties should potentially translate to favourable cardiovascular outcomes in our T2DM patients. There are a number of cardiovascular outcome trials underway with different medications in this class which should be available over the next few years [3 && ]. The most common and important adverse effects include urinary and genital infections and a small increase in bladder and breast cancer, although long-term studies are needed to quantify this risk [6 & ]. Incretin-based agents to lower blood glucose are another recent addition to diabetes therapies. Both the glucagon-like peptide (GLP)-1 analogues