Pregnancy loss and neonatal death in women with type 1 or type 2 diabetes mellitus

Background: Diabetes mellitus (DM) is known to be a significant risk factor for pregnancy loss, either through still-birth or late intrauterine death or as the result of severe congenital malformation. Improved glycemic control and other advances in care substantially reduced the incidence of pregnancy loss in women with type 1 DM in most countries by the 1970s. However, because of a greater prevalence of obesity since the 1980s, the emergence of type 2 DM in pregnancy has become a significant problem. Although more pregnancies now occur in women with type 2 DM than in those with type 1 DM in many locations, relatively little information has been published about pregnancy loss in type 2 DM.Objectives: This article examines the prevalence and causes of pregnancy loss in type 1 and type 2 DM and identifies factors in addition to glycemic control that may influence pregnancy outcome.Methods: A MEDLINE search was conducted for recent literature on pregnancy loss in DM. Series reporting >200 pregnancies in type 1 DM and/or >100 pregnancies in type 2 DM were included.Results: Thirty-four studies were identified (15 in type 1 DM [1997-2007], 19 in type 2 DM [1986-2007]). In type 1 DM, major congenital anomalies now account for ~50% of pregnancy losses, and all-cause perinatal mortality remains higher than in the general population. Several studies have suggested that the perinatal mortality rate is higher in type 2 DM than in type 1 DM. Factors other than glycemic control probably explain this phenomenon: women with type 2 DM typically are older and more obese, and they come from disadvantaged communities—all risk factors for pregnancy loss, particularly late intrauterine death and chorioamnionitis. In some women, type 2 DM may be recognized for the first time during pregnancy; pregnancies in these women carry the same risks of pregnancy loss as those in women with established DM.Conclusions: Demographic changes in the prevalence of obesity suggest that the prevalence of type 2 DM in pregnancy will almost certainly increase. Although meticulous glycemic control is undoubtedly important in achieving good pregnancy outcomes, clinicians should be aware of the multiple risk factors faced by women with DM.     

De-Intensification of Diabetes Treatment in Elderly Patients with Type 2 Diabetes Mellitus

Objective: De-intensification of diabetes treatment is recommended in elderly patients with tight glycemic control at high risk of hypoglycemia. However, rates of de-intensification in endocrine practice are unknown. We conducted a retrospective study to evaluate the rate of de-intensification of antidiabetic treatment in elderly patients with type 2 diabetes mellitus (T2DM) and tight glycemic control.Methods: All patients with ≥2 clinic visits over a 1-year period at a major academic diabetes center were included. De-intensification of diabetes treatment was defined as a decrease or discontinuation of any antidiabetic drug without adding another drug, or a reduction in the total daily dose of insulin or a sulfonylurea drug with or without adding a drug without risk of hypoglycemia.Results: Out of 3,186 unique patients, 492 were ≥65 years old with T2DM and hemoglobin A1c (HbA1c) <7.5% (<58 mmol/mol). We found 308 patients treated with a sulfonylurea drug or insulin, 102 of whom had hypoglycemia as per physician note. Among these 102 patients, 38 (37%) were advised to de-intensify therapy. In a subgroup analysis of patients ≥75 years old with HbA1c <7% (<53 mmol/mol), we found that out of 23 patients treated with a sulfonylurea drug or insulin and reporting hypoglycemia, 11 (43%) were advised de-intensification of therapy. There were no significant predictors of de-intensification of treatment.Conclusion: Our study suggests that de-intensification of antidiabetic medications is uncommon in elderly patients with T2DM. Strategies may need to be developed to prevent the potential harm of overtreatment in this population.Abbreviations: ADA = American Diabetes Association; CGM = continuous glucose monitoring; HbA1c = hemoglobin A1c; T2DM = type 2 diabetes mellitus; UKPDS = United Kingdom Prospective Diabetes Study     

Glycemic Control and Diabetic Dyslipidemia in Adolescents with Type 2 Diabetes

ObjectiveThe incidence of type 2 diabetes mellitus (T2DM) is increasing at an alarming rate, especially in ethnic minorities, and T2DM is associated with significant comorbidities. The primary objective of this study was to assess glycemic control and cardiovascular risk outcomes in children with T2DM at 1 year after diagnosis. We also assessed whether insulin treatment at onset of diabetes is beneficial for overall outcome in those with elevated glycated hemoglobin (HbA1C).MethodsA retrospective electronic chart review of non-Hispanic white (NHW) and African American (AA) children with T2DM.ResultsA total of 86 patients (66.3% females, 79.1% AA, mean age, 13.8 ± 2.4 years) with T2DM were included. Analyses of therapeutic outcome measures at the 1-year follow-up showed HbA1C <8% in 27.7% of patients, low-density-lipoprotein cholesterol (LDL-C) >130 mg/dL in 12.5%, non-high-density-lipoprotein cholesterol (non-HDL-C) >160 mg/dL in 15.6%, HDL-C <35 mg/dL in 25%, systolic hypertension (HTN) in 35.6%, and diastolic HTN in 6.8% of subjects. Among those started on insulin at initial diagnosis, there was significant improvement in glycemic outcomes (P<.0001 on insulin vs. P = .02 not on insulin) and dyslipidemia (total cholesterol [TC] [P = .001], LDL-C [P = .02], HDL-C [P = .01], non-HDL-C [P = .0002], and TC/HDL-C [P = .005]) compared with no significant change among those who did not receive insulin at diagnosis.ConclusionSubstantial numbers of children with T2DM do not achieve glycemic and cardiovascular therapeutic goals 1 year after diagnosis. Insulin therapy at diagnosis has significant beneficial effects on diabetic dyslipidemia in those with higher HbA1C. (Endocr Pract. 2013; 19:972-979)     

Pramlintide as an Adjunct to Basal Insulin: Effects on Glycemic Control and Weight in Patients with Type 2 Diabetes Mellitus

Background: Pramlintide is a synthetic analogue of the β-cell hormone amylin. When used as an adjunct to mealtime insulin, it reduces postprandial glucose concentrations, glycosylated hemoglobin (AIC) values, and weight. Due to its effects on postprandial glucose, pramlintide may also provide similar benefits when used as an adjunct to basal insulin in the absence of mealtime insulin in patients with type 2 diabetes mellitus (DM).Objective: The current post hoc analyses examined the efficacy and tolerability of pramlintide as an adjunct to basal insulin in a subset of patients with type 2 DM in 2 clinical trials.Methods: Post hoc analyses of 2 subgroups of patients with type 2 DM treated with pramlintide and basal insulin (with or without oral agents) with no mealtime insulin are reported. One subgroup of patents was from a 52-week, randomized, double-blind, placebo-controlled study; a second subgroup of patients was from an uncontrolled, open-label study. Mean (SE) changes from baseline in A1C, postprandial glucose, weight, and insulin dose are reported. Tolerability was also assessed.Results: Baseline characteristics (mean [SD]) of the placebo-controlled study were as follows: pramlintide—n = 18; age, 59 (11) years; A1C, 9.4% (1.3%); weight, 88.4 (16.5) kg; body mass index (BMI), 31.8 (6.1) kg/m²; placebo—n = 11; age, 56 (9) years; A1C, 9.4% (1.6%); weight, 92.0 (13.4) kg; and BMI, 31.2 (5.1) kg/m². Baseline characteristics (mean [SD]) of the patients from the open-label study were as follows: N = 10; age, 60 (12) years; A1C, 8.1% (1.3%); weight, 109.2 (26.6) kg; and BMI, 35.7 (8.1) kg/m². In the placebo-controlled study, pramlintide treatment (120 μg BID) as an adjunct to basal insulin (neutral protamine Hagedorn, lente, or ultralente) resulted in mean (SE) reductions in A1C (pramlintide, -1.16% [0.22%]; placebo, -0.48% [0.18%]; P < 0.05) and weight (pramlintide, -2.3 [1.0] kg; placebo, -0.9 [1.0] kg) compared with placebo. Similarly, in the open-label study, pramlintide treatment (120 μg before major meals) as an adjunct to insulin glargine resulted in mean (SE) reductions from baseline in AIC (-0.81% [0.26%]; 95% CI, -1.40 to -0.22) and weight (-2.8 [1.0] kg; 95% CI, -5.12 to -0.47). In addition, mean postprandial glucose excursions, ascertained by self-monitoring of blood glucose readings, were reduced after each meal. In both subgroups, pramlintide was generally well tolerated, and there were no episodes of severe hypoglycemia.Conclusion: The improvements in glycemic control and weight in these post hoc analyses warrant further clinical investigation into the use of pramlintide as a potential next therapeutic step in patients with type 2 DM treated with basal insulin.     

Insulin Therapy and Hypoglycemia in Type 2 Diabetes Mellitus

Background: Iatrogenic hypoglycemia, the limiting factor in the glycemic management of diabetes mellitus (DM), is the result of therapeutic insulin excess and compromised physiological and behavioral defenses against falling plasma glucose concentrations.Objective: The goal of this article was to review the available evidence on insulin therapy and hypoglycemia, with a focus on type 2 DM.Methods: This review was based on the author's clinical experience, his >3 decades of translational research in the area of hypoglycemia, and his knowledge of the relevant preclinical and clinical literature.Results: Glycemic defenses become compromised rapidly in type 1 DM but slowly in type 2 DM. As a result, the frequency of hypoglycemia increases progressively as patients approach the insulin-deficient end of the spectrum of type 2 DM. Indeed, it appears that most episodes of hypoglycemia, including those of severe hypoglycemia, occur in individuals with type 2 DM. The conventional risk factors for hypoglycemia are based on relative or absolute insulin excess. It is clear that the pathogenesis of hypoglycemia-associated autonomic failure, and thus an increased risk for iatrogenic hypoglycemia, stems fundamentally from insulin deficiency. Relevant additional risk factors include the degree of insulin deficiency, a history of severe hypoglycemia, hypoglycemia unawareness, or both, as well as recent antecedent hypoglycemia, prior exercise and sleep, and aggressive glycemic therapy per se in advanced type 2 DM, just as in type 1 DM. The prevention of hypoglycemia involves the practice of hypoglycemia risk reductionȔdiscussion of the issue, application of the principles of aggressive therapy, and consideration of both the conventional risk factors and those relevant to compromised glycemic defensesȔin advanced type 2 DM, just as in type 1 DM. With this approach, it is possible to improve glycemic control and reduce the frequency of hypoglycemia in many people with DM.Conclusions: Pending the prevention and cure of DM, people with this disease need safe and effective therapies. Ultimately, that will require glucose-regulated insulin replacement or secretion. In the meantime, insight into the mechanisms of hypoglycemia-associated autonomic failure may lead to interventions that will further improve the lives of people affected by DM by reducing the frequency of hypoglycemia without compromising glycemic control.(Insulin. 2007;2:127-133)     

The Association of Decreased Serum Gdnf Level with Hyperglycemia and Depression in Type 2 Diabetes Mellitus

Objective: Comorbidity of diabetes and depression is a critical problem. Decreased glial-derived neurotrophic factor (GDNF) has been demonstrated in depression, but no evidence of a relationship between GDNF and diabetes has been shown. The present studies were designed to investigate the relationship between GDNF and metabolism.Methods: In Study 1, we performed a case-control study in which subjects with type 2 diabetes mellitus (T2DM), prediabetes (p-DM), and normal glucose tolerance (NGT) were included. In Study 2, we performed a cross-sectional study in 296 patients having pre-existing diabetes in whom the levels of serum GDNF, blood glucose, blood lipids, blood pressure, body mass index, scores from the Patient Health Questionnaire (PHQ-9), the EuroQol-5 scale, and the diabetes distress scale were measured, as well as single-nucleotide polymorphisms of GDNF including rs884344, rs3812047, and rs2075680.Results: In Study 1, serum GDNF concentration was significantly lower in the T2DM group than in the NGT group (NGT: 11.706 ± 3.918 pg/mL; p-DM: 10.736 ± 3.722 pg/mL; type 2 diabetes mellitus &lsqb;T2DM group]: 9.884 ± 2.804 pg/mL, P = .008). In Study 2, significantly decreased serum GDNF levels were observed in subjects with poor glycemic control or depression (glycated hemoglobin &lsqb;HbA1c] <7.0% without depression: 11.524 ± 2.903 pg/mL; HbA1c ≥7.0% without depression: 10.625 ± 2.577 pg/mL; HbA1c <7.0% with depression: 10.355 ± 2.432 pg/mL; HbA1c ≥7.0% with depression: 8.824 ± 2.102 pg/mL, P = .008). Double-factor variance analysis showed that glycemic control and depression were independent factors for the GDNF level. Moreover, the serum GDNF level was significantly inversely associated with the fasting plasma glucose, 2 hours postprandial plasma glucose, HbA1c, and PHQ-9 score.Conclusion: Glycemic dysregulation was an independent factor for the GDNF level. These findings suggest that GDNF level might be involved in the pathophysiology of T2DM and depression through various pathways.Abbreviations: BP = blood pressure; CHO = cholesterol; DDS = diabetes distress scale; DM = diabetes mellitus; EQ-5D = the health-related dimensions of the EuroQol-5 scale; FPG = fasting plasma glucose; GDNF = glial-derived neurotrophic factor; HbA1c = glycated hemoglobin; HDL = high-density lipoprotein; LDL = low-density lipoprotein; NGT = normal glucose tolerance; PHQ-9 = Patient Health Questionnaire; p-DM = prediabetes; PPG = postprandial plasma glucose; SNP = single-nucleotide polymorphism; T2DM = type 2 diabetes mellitus; TG = triglyceride     

Advanced Insulin Management program reduces A1C levels and regimen-related distress without weight gain in patients with type 1 diabetes mellitus

Background: Despite the availability of effective treatments, many patients with diabetes have suboptimal glycemic control.Objective: This study was designed to determine whether the Advanced Insulin Management (AIM) program could help patients with type 1 diabetes mellitus (DM) reduce their A1C levels to ≤7.5% without weight gain, increased incidence of hypoglycemia, or increased diabetes-related distress.Methods: The AIM program, developed to intensify glycemic control in patients with type 1 DM, consisted of a screening visit and 3 to 6 interactive group sessions, depending on whether the patient elects multiple daily injections (MDIs) or an insulin pump. Patients who wanted to learn additional diabetes management skills were referred by their endocrinologist, and those with competent carbohydrate-counting skills and record-keeping practices were eligible to enroll. A nurse, dietitian, psychologist, and physician provided group instruction and supported individual goal setting. The program included depression screening, regimen adjustments, and problem-solving activities. Outcome measures, including blood glucose, A1C, weight, and diabetes-related distress, were tracked for 12 months.Results: The study included 113 adult patients with type 1 DM (59% female; mean age, 39 years). Twenty patients already had insulin pumps, 46 patients initiated pump therapy during the study, and 47 patients elected MDIs. Mean A1C declined by 0.5% (to 7.3%) after 12 months, without weight gain or increased hypoglycemia. A significant decrease in diabetes-related distress was observed.Conclusion: The AIM program was associated with important improvements in glycemic control in patients with type 1 DM, without weight gain or increased hypoglycemic episodes.     

Weight Gain and Management Concerns in Patients on Insulin Therapy

Background: The benefits of tight glycemic control in preventing the onset and progression of microvascular complications in patients with type 2 diabetes mellitus (DM) are unarguable. The majority of patients with type 2 DM will eventually require insulin to achieve adequate glycemic control. Using insulin earlier rather than later in the course of type 2 DM may diminish the deleterious effects of hyperglycemia on β-cell function and therefore help prolong good glycemic control and prevent the occurrence of microvascular complications. However, weight gain is a potential adverse effect of insulin therapy.Objective: The goal of this article was to describe the benefit of insulin therapy early in the course of type 2 DM, review the association of weight gain with insulin therapy, and examine potential detrimental effects that insulin-associated weight gain could have in patients with type 2 DM.Methods: Materials used for this article were identified through a search of MEDLINE (1966–2006). English-language articles were chosen using the search terms diabetes mellitus type 2, insulin, and obesity.Results: Intensive insulin therapy is often associated with weight gain. Although there is concern that weight gain in patients with type 2 DM may have adverse effects on risk factors for cardiovascular disease, unfavorable changes in blood pressure and lipid levels have not been consistently observed in clinical trials. Furthermore, clinical evidence, including data from the United Kingdom Prospective Diabetes Study, supports the view that intensive insulin therapy does not increase the risk for cardiovascular disease.Conclusions: Early insulin therapy in patients with type 2 DM may be a strategy that will help patients achieve and maintain good glycemic control, thereby reducing the risk of developing microvascular complications. Although weight gain is commonly associated with insulin therapy, it does not appear to put these patients at greater risk for cardiovascular disease.     

Patients Achieving Good Glycemic Control (HBA1c <7%) Experience A Lower Rate of Hypoglycemia With Insulin Degludec Than with Insulin Glargine: A Meta-Analysis of Phase 3A Trials

Objective: Meta-analysis to compare hypoglycemia rates of basal insulin degludec (IDeg) with insulin glargine (IGlar) in patients with diabetes achieving good glycemic control (hemoglobin A_1c [HbA_1c] <7% at end of trial).Methods: In a preplanned meta-analysis, patient data from 7 randomized, treat-to-target, 26- or 52-week trials in patients with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) who administered IDeg (n = 2,899) or IGlar (n = 1,431) once daily were analyzed. Using a negative binomial regression model, this meta-analysis compared hypoglycemia rates in patients achieving HbA_1c <7% at end of trial with IDeg (n = 1,347) and IGlar (n = 697).Results: In all trials, IDeg was noninferior to IGlar in HbA_1c reduction from baseline. At end of trial, 2,044 patients (T2DM, n = 1,661; T1DM, n = 383) achieved HbA_1c <7%. The overall confirmed hypoglycemia rate, defined as plasma glucose <56 mg/dL or severe hypoglycemia if requiring assistance, was significantly lower with IDeg versus IGlar (estimated rate ratio [ERR] IDeg:IGlar, 0.86; 95% confidence interval [CI], 0.76 to 0.98). The nocturnal confirmed hypoglycemia rate, defined as occurring between midnight and 6:00 am, was significantly lower with IDeg (ERR, 0.63; 95% CI, 0.52 to 0.77). In the maintenance period (16 weeks onward when average insulin dose and glycemic levels stabilized), the overall confirmed hypoglycemia rate was significantly lower (ERR, 0.79; 95% CI, 0.68 to 0.92) and the nocturnal confirmed hypoglycemia rate was significantly lower (ERR, 0.57; 95% CI, 0.45 to 0.72) with IDeg versus IGlar.Conclusion: Patients with T1DM and T2DM achieved HbA_1c <7% with significantly lower rates of overall and nocturnal confirmed hypoglycemia with IDeg versus IGlar. The lower hypoglycemia rate with IDeg was more pronounced in the maintenance period.Abbreviations: ERR = estimated rate ratio; HbA_1c = hemoglobin A_1c; IDeg = insulin degludec; IGlar = insulin glargine; NPH = Neutral Protamine Hagedorn; PG = plasma glucose; T1DM = type 1 diabetes mellitus; T2DM = type 2 diabetes mellitus     

Comparison of Basal Insulin Regimens on Glycemic Variability in Noncritically Ill Patients with Type 2 Diabetes

Objective: To evaluate the impact of different subcutaneous basal insulin regimens on glycemic variability (GV) and hospital complications in non-intensive care unit (ICU) patients with type 2 diabetes (T2D).Methods: This study is a post hoc analysis of 279 general medicine and surgery patients treated with either a “Basal Bolus” insulin regimen using glargine once daily and glulisine before meals or a “Basal Plus” regimen using glargine once daily plus correction doses of glulisine before meals for glucose >140 mg/dL. GV was calculated as mean delta (Δ) daily glucose, mean SD, and mean amplitude of glycemic excursions (MAGE).Results: Treatment with Basal Bolus and Basal Plus regimens resulted in similar mean daily glucose, hypoglycemia, length of stay (LOS), and hospital complications (all P>.05). There were no differences in GV between treatment groups by Δ change (72.5 ± 36 vs. 69.3 ± 34 mg/dL), SD (38.5 ± 18 vs. 37.1 ± 16 mg/dL) and MAGE (67.5 ± 34 vs. 66.1 ± 39 mg/dL) (all P>.05). Surgery patients treated with Basal Bolus had higher GV compared to those treated with Basal Plus (Δ daily glucose and SD: P = .02, MAGE: P = .009), but no difference in GV was found between treatment groups for the general medicine patients (P>.05). Patients with hypoglycemia events had higher GV compared to subjects without hypoglycemia (P<.05), but no association was found between GV and hospital complications (P>.05).Conclusion: Treating hospitalized, non-ICU, diabetic patients with Basal Plus insulin regimen resulted in similar glucose control and GV compared to the standard Basal Bolus insulin regimen. Higher GV was not associated with hospital complications.Abbreviations:BG = blood glucoseCV= coefficient of variationGV= glycemic variabilityICU = intensive care unitLOS = length of stayMAGE = mean amplitude of glycemic excursionsSSI = sliding scale insulinT2D = type 2 diabetesTDD =total daily dose     

The Use of Premixed Insulin Analogues in the Treatment of Patients with Type 2 Diabetes Mellitus: Advantages and Limitations

Background:Intensive, target-oriented therapy is the standard of care in the management of patients with type 2 diabetesmellitus (DM). Early and aggressive use of insulin that is as close as possible to the physiologic pattern of insulin secretion from healthy pancreatic β-cells is advocated to achieve glycemic goals and reduce complications of DM.Objective:The objective of this article was to review the characteristics, advantages, and drawbacks of premixedinsulin analogues and to evaluate their role in the treatment of patients with type 2 DM.Methods:A PubMed search of articles from 1990 to 2006 was undertaken using the search terms type 2 diabetes, basalbolus therapy, premixed insulins, biphasic insulins, and insulin analogues. Pertinent content from relevant articles was extracted and combined with the authors' knowledge, experience, and clinical expertise.Results:The advent of insulin analogues has streamlined the treatment of patients with DM. When to initiate insulin during the course of treatment is the subject of much debate. Insulin therapy targeting both fasting and postprandial hyperglycemia is important in achieving optimal blood glucose (BG) control in patients with type 2 DM. A practical and feasible option is the use of >1 injection of premixed insulin analogues. Premixed insulin preparations provide both basal and prandial coverage because of their biphasic pharmacokinetic properties. Clinical trials have shown that these agents improve glycemic control, are associated with an acceptably low rate of severe hypoglycemia, and have a high degree of patient acceptance. Limitations include the inability to adjust the long- and short-acting components separately, to use a flexible regimen of self-titration and premeal bolus-insulin calculations, and to adequately treat postlunch and earlymorning BG elevations.Conclusion:Clinicians should be aware of premixed insulin analogues' advantages and limitations so that these agentscan be used appropriately in the treatment of patients with type 2 DM.     

Clinical Outcomes Using Long-Term Combination Therapy with Insulin Glargine and Exenatide in Patients with Type 2 Diabetes Mellitus

ObjectiveTo examine the long-term effects of combination insulin glargine/exenatide treatment on glycemic control.MethodsWe conducted a 24-month retrospective US chart review of patients with inadequately controlled type 2 diabetes (T2DM) and hemoglobin A_1c (A1C) levels > 7.0% for whom glargine and exenatide were coprescribed in differing order (glargine added after exenatide [exenatide/glargine]; exenatide added after glargine [glargine/exenatide]). Treatment order groups were combined to form a pooled treatment group. Changes from baseline in A1C, patients with A1C ≤ 7.0%, body weight, glargine/exenatide daily dose, oral antidiabetic drug (OAD) use, and hypoglycemia were evaluated.ResultsTreatment groups were similar at baseline; however, patients in the glargine/exenatide group (n = 121) (vs exenatide/glargine group [n = 44]) had longer disease duration (11.8 vs 8.0 years) and took fewer OADs (1.7 vs 2.3). Overall, baseline A1C was 8.8 ± 1.3% and weight was 109.5 ± 25.3 kg. Significant A1C reductions emerged at month 6 and persisted throughout 24 months (vs baseline) in both treatment groups (pooled: –0.7 ± 1.6; P < .001), and 33.0% of patients achieved an A1C level ≤ 7.0%. After 24 months of exenatide/glargine, body weight remained unchanged (0.7 ± 8.3 kg; P = .640). With glargine/exenatide, body weight decreased (–2.5 ± 6.7 kg; P = .001). At month 24, daily glargine dose was 0.40 ± 0.23 units/kg for the exenatide/glargine group and 0.47 ± 0.30 units/kg for the glargine/exenatide group. Hypoglycemia frequency was similar in both treatment groups.ConclusionsRegardless of treatment order, long-term combined therapy with glargine and exenatide for up to 24 months in patients with inadequately controlled T2DM suggests reduction of A1C without significant weight gain or increased hypoglycemia risk. (Endocr Pract. 2012;18:17-25)     

Incorporating postprandial and fasting plasma glucose into clinical management strategies

Background: Targeting plasma glucose is a widely accepted practice in the treatment of both type 1 and type 2 diabetes mellitus (DM). Although clinicians have traditionally relied on fasting plasma glucose (FPG) levels for diagnosis and as a target for therapy, the focus has expanded to include the contribution of postprandial glucose (PPG) to glycosylated hemoglobin (A1C) levels.Objective: This article examines the contributions of FPG and PPG to A1C levels in patients with diabetes and discusses the impact of these findings on insulin treatment strategies for patients who fail to achieve recommended A1C goals.Methods: Relevant articles were identified through a PubMed search of the literature (1975–2007) using the following search terms: fasting plasma glucose, postprandial glucose, postprandial hyperglycemia, and glycemic control.Results: Changes in PPG levels are typically the first signs of abnormal glucose metabolism associated with type 2 DM, and they are a useful measure of glycemic control in patients with near-normal FPG and high A1C levels. A substantial proportion of patients considered to have good glycemic control (A1C <7.0%) may continue to experience elevated PPG levels, which have been linked to an increased risk of cardiovascular disease. FPG levels may predict the degree of postprandial hyperglycemia and the extent of PPG excursion. Conversely, correction of PPG levels may reduce FPG levels by suppressing hepatic glucose production. Evidence indicates that therapy targeting both FPG and PPG is associated with optimal reductions in A1C levels. At very high A1C levels (>9%-10%), FPG may play a greater role in overall glucose control than does PPG, but PPG becomes a more important contributor as A1C levels decrease. Increasing evidence supports the long-term benefits of early initiation of intensive insulin therapy. In particular, prandial insulin therapy may address the issue of postprandial hyperglycemia, which may be insufficiently controlled with oral agents and/or basal insulin alone.Conclusions: Both FPG and PPG affect A1C levels and are important contributors to determining overall glycemic control. Alternative insulin therapies (eg, inhaled insulin) that minimize barriers to insulin therapy and the appropriate targeting of FPG and PPG levels may improve long-term outcomes in patients with diabetes.     

Risk Factors for Hypoglycemia in Inpatients with Total Parenteral Nutrition and Type 2 Diabetes: A Post HOC Analysis of the Insupar Study

Objective: Treatment of hyperglycemia with insulin is associated with increased risk of hypoglycemia in type 2 diabetes mellitus (T2DM) patients receiving total parenteral nutrition (TPN). The aim of this study was to determine the predictors of hypoglycemia in hospitalized T2DM patients receiving TPN.Methods: Post hoc analysis of the INSUPAR study, which is a prospective, open-label, multicenter clinical trial of adult inpatients with T2DM in a noncritical setting with indication for TPN.Results: The study included 161 patients; 31 patients (19.3%) had hypoglycemic events, but none of them was severe. In univariate analysis, hypoglycemia was significantly associated with the presence of diabetes with end-organ damage, duration of diabetes, use of insulin prior to admission, glycemic variability (GV), belonging to the glargine insulin group in the INSUPAR trial, mean daily grams of lipids in TPN, mean insulin per 10 grams of carbohydrates, duration of TPN, and increase in urea during TPN. Multiple logistic regression analysis showed that the presence of diabetes with end-organ damage, GV, use of glargine insulin, and TPN duration were risk factors for hypoglycemia.Conclusion: The presence of T2DM with end-organ damage complications, longer TPN duration, belonging to the glargine insulin group, and greater GV are factors associated with the risk of hypoglycemia in diabetic noncritically ill inpatients with parenteral nutrition.Abbreviations: ADA = American Diabetes Association; BMI = body mass index; CV% = coefficient of variation; DM = diabetes mellitus; GI = glargine insulin; GV = glycemic variability; ICU = intensive care unit; RI = regular insulin; T2DM = type 2 diabetes mellitus; TPN = total parenteral nutrition     

Case Finding for Hypothyroidism Should Include Type 2 Diabetes and Metabolic Syndrome Patients: A Latin American Thyroid Society (LATS) Position Statement

Objective: Latin American Thyroid Society (LATS) Hypothyroidism Clinical Practice Guidelines recommend case finding of hypothyroid patients in multiple and different situations that agree with other Society guidelines. However, the detection of hypothyroidism in type 2 diabetes mellitus (T2DM) or metabolic syndrome (MetS) patients is not mentioned in particular. In the recent years, several basic and epidemiologic studies have appeared showing that a lower thyroid function and MetS/T2DM are associated. Hence, the aim of this review is to manifest the LATS position on the diagnosis of hypothyroidism in both MetS and T2DM patients.Methods: A search was made in PubMed using the following terms: “hypothyroidism” AND “diabetes” OR “metabolic syndrome.” The most relevant studies describing the prevalence and complications due to hypothyroidism in both MetS and T2DM patients were selected.Results: The current document reviews new information from studies that have shown that the prevalence of hypothyroidism is higher in T2DM patients (odds ratio &lsqb;OR], 3.45; 95% confidence interval &lsqb;CI], 2.5 to 4.7) and that diabetic complications are more prevalent in subclinical hypothyroidism (ScH). The incidence of T2DM is 1.09-fold higher with each doubling of thyroid-stimulating hormone (TSH) mIU/L (95% CI, 1.06 to 1.12), and the incidence of prediabetes increases 15% (hazard ratio, 1.15; 95% CI, 1.04 to 1.26) in patients with TSH >5 mIU/L. Similarly, MetS is more prevalent in ScH compared to euthyroid individuals (OR, 1.31; 95% CI, 1.08 to 1.60).Conclusion: Thyroid function is affected in MetS and T2DM, and hypothyroidism is more common in these patients. Diabetic complications are more frequent in ScH patients. Therefore, LATS now recommends aggressive case finding of hypothyroidism in both MetS and T2DM patients.Abbreviations: CI = confidence interval; GLUT4 = glucose transporter 4; HOMA-IR = homeostatic model assessment for insulin resistance; HR = hazard ratio; LATS = Latin American Thyroid Society; MetS = metabolic syndrome; OR = odds ratio; ScH = subclinical hypothyroidism; T2DM = type 2 diabetes mellitus; T3 = triiodothyronine; T4 = thyroxine; TSH = thyroid-stimulating hormone     

Does Clinical Inertia Vary By Personalized A1C Goal? A Study Of Predictors And Prevalence Of Clinical Inertia In A U.S. Managed Care Setting

Objective: Clinical inertia is defined as failure to initiate or intensify therapy despite an inadequate treatment response. We assessed the prevalence and identified the predictors of clinical inertia among patients with type 2 diabetes (T2DM) based on personalized goals.Methods: Three hemoglobin A_1c (A1C) targets (American Diabetes Association A1C <7.0%; modified Ismail-Beigi et al; and Healthcare Effectiveness Data and Information Set) were used when identifying adult patients with T2DM who experienced above-target A1C values during the index period (July 1, 2008 to June 30, 2012) in a U.S. managed-care claims database (IMPACT™). Clinical inertia was defined as no intensification of treatment during the response period. Demographic and clinical characteristics were analyzed to identify predictors of treatment intensification.Results: Irrespective of A1C target, the majority of patients with T2DM (70.4 to 72.8%) experienced clinical inertia in the 6 months following the index event, with 5.3 to 6.2% of patients intensifying treatment with insulin. Patients with a lower likelihood of intensification were older, used >1 oral antidiabetes drug during the baseline period, and had an above-target A1C more recently. Treatment intensification was associated with patients who had point-of-service insurance, mental illness, an endocrinologist visit in the baseline period, or higher index A1C.Conclusion: The prevalence of clinical inertia among patients with T2DM in a U.S. managed-care setting is high and has increased over more recent years. Factors predicting increased risk of clinical inertia may help identify “at-risk” populations and assist in developing strategies to improve their management.Abbreviations:A1C = hemoglobin A_1cADA = American Diabetes AssociationCCI = Charlson Comorbidity IndexGLP-1 = glucagon-like peptide 1HEDIS = Healthcare Effectiveness Data and Information SetICD-9-CM = International Classification of Diseases, 9th Revision, Clinical ModificationOAD = oral antidiabetes drugPCPs = primary care physiciansT2DM = type 2 diabetes mellitus     

Glycemic Effects Of Sglt-2 Inhibitor Canagliflozin In Type 1 Diabetes Patients Using The Dexcom G4 Platinum Cgm

Objective: Limited information is available on chronic use of sodium glucose cotransporter 2 inhibitors in type 1 diabetes (T1D). We conducted a retrospective review of T1D patients on Dexcom G4Platinum continuous glucose monitors (DCGMs) >1 year (mean, 4.6 years) who were prescribed canagliflozin (CANA) 100 mg daily and had a baseline DCGM 30-day download prior to and a second download after at least 1 month (mean, 3.7 months) taking CANA 100 mg daily. The glycemic, weight, and systolic blood pressure (SBP) effects are reported.Methods: We identified 27 patients meeting the selection criteria: 14 men; 25 white; 22 on pump; average T1D duration, 34 years (range, 12 to 48 years); average hemoglobin A1C (A1C), 7.6% (range, 6.1 to 9.8%); 22 with baseline A1C 7.0% or higher. All patients had an estimated glomerular filtration rate (eGFR) at baseline of 60 mL/min/1.73 m² or higher and were normotensive or on stable therapy. On average, 29 days of CGM data was reviewed. Total daily insulin dose (TDD) was available in 21 patients. We identified 27 patients who were judged to be candidates for CANA but did not have any change in glycemic therapy other than insulin adjustment as controls.Results: CANA resulted in significant reductions in mean blood glucose, CGM standard deviation, time in hyperglycemia, A1C, weight, SBP, and TDD, with increased time in target, with minimal increase in hypoglycemia and no significant change in eGFR. Three females developed genital mycotic infections but continued therapy, 2 developed ketoacidosis from insulin interruption.Conclusion: CANA offers promise as adjunct therapy in T1D, though caution is advised.Abbreviations:A1C = hemoglobin A1CCANA = canagliflozinCGM = continuous glucose monitorCSII = continuous subcutaneous insulin infusionDCGM = Dexcom G4Platinum CGMDKA = diabetic ketoacidosisGMI = genital mycotic infectionMG = mean glucosePCGM = personal continuous glucose monitoringSBP = systolic blood pressureSGLT-2i = sodium-glucose cotransporter 2 inhibitorSH = severe hypoglycemiaT2D = type 2 diabetesT1D = type 1 diabetes     

Clinical Characteristics of Patients with Type 2 Diabetes Mellitus Continued on Oral Antidiabetes Medications in the Hospital

Objective: Basal/basal-bolus insulin with discontinuation of home oral antidiabetes medications (OADs) is the preferred method to achieve glycemic control in many hospitalized patients. We hypothesized that a subset of patients with type 2 diabetes mellitus (T2DM) can achieve an acceptable level of blood sugar control without cessation of their OADs when hospitalized.Methods: A retrospective chart review was conducted on patients with T2DM who were only on OADs at home, admitted to Fairview Hospital, a community hospital in the Cleveland Clinic Health System. We divided patients into those whose OADs were continued (group 1) and those whose OADs were discontinued (group 2), with or without the addition of insulin in the hospital. Blood glucose (BG) levels and patient characteristics were compared.Results: There were 175 patients, 73 in group 1 and 102 in group 2. The percentage of patients achieving all BG values within 100 to 180 mg/dL was the same between group 1 (21.9%) and group 2 (23.8%) (P = .78). Mean BG was similar between group 1 and group 2 (146.1 ± 41.4 mg/dL versus 152.1 ± 38.9 mg/dL; P = .33), with no significant difference in terms of percentage of patients with hyperglycemia or hypoglycemia. A greater proportion of patients in group 1 had an uninterrupted feeding status, nonintensive care unit admission and no contrast dye exposure, and a shorter length of stay.Conclusion: Our study shows that patients with certain characteristics could achieve an acceptable level of glycemic control without cessation of their home OADs.Abbreviations: BG = blood glucose; DPP-4 = dipeptidyl dipeptidase 4; GFR = glomerular filtration rate; HbA1c = hemoglobin A1c; ICU = intensive care unit; LOS = length of stay; NPO = nil per os; OAD = oral antidiabetes medication; POC = point of care; T2DM = type 2 diabetes mellitus     

The Added and Interpretative Value of CGM-Derived Parameters in Type 1 Diabetes Depends on the Level of Glycemic Control

ObjectiveIn type 1 diabetes mellitus (T1DM) management, continuous glucose monitoring (CGM)-derived parameters can provide additional insights, with time in range (TIR) and other parameters reflecting glycemic control and variability being put forward. This study aimed to examine the added and interpretative value of the CGM-derived indices TIR and coefficient of variation (CV%) in T1DM patients stratified according to their level of glycemic control by means of HbA1C.MethodsT1DM patients with a minimum disease duration of 10 years and without known macrovascular disease were enrolled. Patients were equipped with a blinded CGM device for 7 days. TIR and time spent in hypoglycemia and hyperglycemia were determined, and CV% was used as a parameter for glycemic variability. Pearson (r) and Spearman correlations (r_s) and a regression analysis were used to examine associations.ResultsNinety-five patients (age: 45 ± 10 years; HbA1C level: 7.7% ± 0.8% [61 ± 7 mmol/mol]) were included (mean blood glucose [MBG]: 159 ± 31 mg/dL; TIR: 55.8% ± 14.9%; CV%: 43.5% ± 7.8%) and labeled as having good (HbA1C level ≤7% [≤53 mmol/mol]; n = 20), moderate (7%-8%; n = 44), or poor (>8% [>64 mmol/mol]; n = 31) glycemic control. HbA1C was significantly associated with MBG (r_s = 0.48, P < .001) and time spent in hyperglycemia (total: r_s = 0.52; level 2: r = 0.46; P < .001) but not with time spent in hypoglycemia and CV%, even after an analysis of the HbA1C subgroups. Similarly, TIR was negatively associated with HbA1C (r = −0.53; P < .001), MBG (r_s = −0.81; P < .001), and time spent in hyperglycemia (total: r_s = −0.90; level 2: r_s = −0.84; P < .001) but not with time in hypoglycemia. The subgroup analyses, however, showed that TIR was associated with shorter time spent in level-2 hypoglycemia in patients with good (r_s = −0.60; P = .007) and moderate (r_s = −0.25; P = .047) glycemic control. In contrast, CV% was strongly positively associated with time in hypoglycemia (total: r_s = 0.78; level 2: r_s = 0.76; P < .001) but not with TIR or time in hyperglycemia in the entire cohort, although the subgroup analyses showed that TIR was negatively associated with CV% in patients with good glycemic control (r = −0.81, P < .001) and positively associated in patients with poor glycemic control (r = +0.47; P < .01).ConclusionThe CGM-derived metrics TIR and CV% are related to clinically important situations, TIR being strongly dependent on hyperglycemia and CV% being reflective of hypoglycemic risk. However, the interpretation and applicability of TIR and CV% and their relationship depends on the level of glycemic control of the individual patient, with CV% generally adding less clinically relevant information in those with poor control. This illustrates the need for further research and evaluation of composite measures of glycemic control in T1DM.     

Management of Type 2 Diabetes Mellitus with Basal-Prandial Insulin Therapy: A Case-Based Review

Background: Diabetes mellitus (DM) is a growing epidemic in the United States—20.8 million people are affected and 90% to 95% of all diagnosed cases are type 2 DM. Nevertheless, implementation of insulin therapy is often delayed in patients with type 2 DM. This delay can increase the risk of DM-related complications, including microvascular neuropathy, nephropathy, retinopathy, and cardiovascular disease.Objective: This article provides a case-based review outlining a novel strategy for advancing therapy with a modified basal and prandial insulin regimen to achieve recommended glycemic targets in type 2 DM as quickly as possible. Evidence-based treatment strategies are also discussed.Methods: Materials used for this article were identified through an English-language literature search of MEDLINE (1967-2007) using the following terms: insulin, postprandial glucose control, and type 2 diabetes.Results: As shown with this male 46-year-old case study patient, type 2 DM is treated initially with diet and exercise, followed by oral antidiabetic drugs (OADs). However, oral therapy typically reduces glycosylated hemoglobin values only by -1.5% to 2.0%. Intensive therapy with once-daily basal insulin in combination with a previously prescribed OAD regimen can achieve normoglycemia and reduce the long-term complications of DM. In patients with postprandial glucose excursions, prandial insulin can be added using a rapid-acting insulin analogue (aspart, lispro, or glulisine).Conclusions: A key factor in this case patient's ability to reach glycemic targets within I year of diagnosis of type 2 DM was the accelerated implementation of insulin therapy. Such a therapeutic approach obviates the risk for uncontrolled hyperglycemia, which is associated with the standard practice of beginning treatment with diet and exercise alone and slowly advancing by i OAD at a time, ending with insulin therapy as a last resort. (Insulin. 2007;2:118-126)