Fasting Versus Postprandial Hyperglycemia as a Treatment Target to Lower Elevated Hemoglobin A1C

Objective: Postprandial hyperglycemia (PPHG) may need addressing when glycemic control cannot be maintained in patients with type 2 diabetes mellitus. We investigated whether glycated hemoglobin A_1c (A_1c) levels ≥7.0% can indicate postprandial defects warranting prandial therapy after optimized basal insulin therapy.Methods: From 6 clinical trials of insulin glargine treatment, data were pooled from 496 patients with A_1c ≥7.0% after 24 weeks. Patient characteristics and clinical outcomes were summarized according to fasting plasma glucose (FPG) target achievement (<130 mg/dL), postprandial blood glucose (PPBG) levels, and PPBG increments (ΔPPBG). Basal and postprandial contributions to hyperglycemia were determined.Results: After 24 weeks of insulin glargine titration, A_1c change from baseline was greater in patients with FPG <130 mg/dL versus ≥130 mg/dL (-1.35% versus -1.11%, respectively; P = .0275), but with increased confirmed hypoglycemia rates (blood glucose <70 mg/dL; 4.06 events/patient-year versus 3.31 events/patient-year; P = .0170). However, increased severe hypoglycemia rates were observed in patients with FPG ≥130 mg/dL. At week 24, postprandial contributions to hyperglycemia increased (>60% regardless of PPBG). Patients with high FPG had lower, but substantial, relative postprandial contributions versus patients achieving FPG target. A similar pattern was observed according to whether patients had a ΔPPBG ≥50 mg/dL after any meal.Conclusion: After optimized basal insulin therapy, elevated A_1c is the most effective indicator of residual PPHG, regardless of existent FPG or PPBG. When confronted with an uncontrolled A_1c after reasonable titration of basal insulin, clinicians should be aware of probable postprandial contributions to hyperglycemia and consider prandial therapy.Abbreviations:A_1c = glycated hemoglobin A_1cAUC = area under the curveAUC_B = area under the curve (basal hyperglycemia)AUC_G = total area under the curve (total glucose)AUC_N = area under the curve (normal glycemic exposure)AUC_P = area under the curve (postprandial hyperglycemia)BHG = basal hyperglycemiaFBG = fasting blood glucoseFPG = fasting plasma glucoseGLP-1 = glucagon-like peptide 1HE = hyperglycemic exposureOADs = oral antidiabetes drugsPPBG = postprandial blood glucoseΔPPBG = change in postprandial blood glucosePPHG = postprandial hyperglycemiaSMBG = self-monitored blood glucoseT2DM = type 2 diabetes mellitus     

The role of rapid-acting insulin analogues and inhaled insulin in type 2 diabetes mellitus

sBackground:The availability of rapid-acting insulin analogues and inhaled insulin gives clinicians additional treatmentoptions in the management of patients with diabetes mellitus (DM). Combining rapid-acting insulin analogues with basal insulin can more closely mimic physiologic insulin release to maximize glycemic control.Objective:The objective of this article was to discuss the role of rapid-acting insulin analogues and inhaled insulin inthe treatment of patients with type 2 DM.Methods:Materials for this article were obtained through an online search of MEDLINE/PubMed and Google(1996-2006) using the search terms bolus insulin, postprandial, rapid-acting insulin analogues, titration, hypoglycemia, glycemic control, inhaled insulin, and insulins lispro, aspart, and glulisine.Results:Glycosylated hemoglobin (A1C) levels and number of all hypoglycemic episodes were similar in patients withtype 2 DM taking either mealtime rapid-acting insulin analogues or regular human insulin (RHI). Rapid-acting insulins have been successfully used in basal-bolus regimens with a variety of long- and intermediate-acting insulins, as well as with oral hypoglycemic agents. Injectable rapid-acting insulin analogues markedly decreased postprandial glucose (PPG) levels compared with RHI. Better reduction in PPG levels may be key to achieving target A1C levels in some patients, but long-term outcome studies are needed to assess whether lowering PPG levels decreases cardiovascular risk in patients with type 2 DM. Inhaled insulin may be an option for patients who cannot inject insulin, but route of administration and dosing issues limit its use in many patients. The effect of inhaled insulin on PPG is unclear at this time.Conclusions:Although rapid-acting insulin analogues are effective in the management of patients with type 2 DM, the limited numbers of studies have yet to demonstrate that these agents have any significant long-term advantage compared with RHI. In addition, they cost more than RHI. Further studies are needed to compare the efficacy of the rapid-acting insulin analogues, to compare the different dosing regimens used with mealtime insulin administration, and to ascertain if the decrease in PPG levels seen with the use of rapid-acting insulin analogues translates into improved glycemic control and perhaps even a reduction in cardiovascular risk in patients with type 2 DM. (Insulin. 2007;2:61-67) Copyright 2007 Excerpta Medica, Inc.     

The Rationale for Prandial Glycemic Control in Diabetes Mellitus

Background:Diabetes mellitus (DM) is of epidemic proportions worldwide, and its microvascular and macrovascular complications have been well described. Achieving glycemic control has been demonstrated to reduce patients' risk of developing these complications.Objective:The objective of this article was to examine how prandial hyperglycemia-especially postprandial hyperglycemia (PPHG)-affects overall glycemic control and the complications of DM and to discuss the pharmacologic agents available to reduce PPHG.Methods:Materials used for this article were identified through a MEDLINE search of the literature (1975–2006). English-language randomized, controlled, prospective, cohort, and observational studies were chosen using the search terms postprandial hyperglycemia, oxidative stress, cardiovascular disease, macrovascular disease, microvascular disease, lipidemia, and coagulation.Results:Data show that controlling prandial hyperglycemia reduces the risk of cardiovascular disease (CVD) andmicrovascular complications, lowers glycosylated hemoglobin levels, causes less oxidative stress, and leads to a more favorable coagulation and postprandial lipidemia profile. Guidelines for targeting PPHG are becoming standard, and various pharmacologic agents (eg, a-glucosidase inhibitors, amylin analogues, incretin mimetics, rapid-acting insulins and insulin analogues, meglitinide analogues) that target PPHG may also improve overall glycemic control and reduce CVD risk.Conclusions:Although the level of hyperglycemia that leads to microvascular and macrovascular complications inpatients with DM remains to be elucidated, it appears prudent to address prandial hyperglycemia, especially PPHG, rather than focus solely on fasting glucose levels. Clinicians should consider incorporating agents that lower PPHG in their treatment of patients with DM.     

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)     

Beta cell response to a mixed meal in nigerian patients with type 2 diabetes

ABSTRACT: BACKGROUND: The pathophysiology of type2 diabetes involves both insulin resistance and poor beta cell function. Studies have been done in several populations to assess the relative importance of these mechanisms in individual patients. In our environment studies to assess beta cell function have been done with glucagon stimulation or an oral glucose tolerance test. This study was done to assess the response of the beta cell to a standardized mixed meal and its relationship with glycaemic control in patients with type2 diabetes. METHODS: Ninety patients with type 2 diabetes were recruited into the study. Weight, height, body mass index and waist circumference were measured. Blood samples were analysed for fasting plasma glucose (FPG) and fasting C peptide (FCP) and glycated haemoglobin (HbA1c). Patients were given their usual drugs for management of their diabetes and then served with a standard meal calculated to contain 50 g of carbohydrate, made up of 53 % carbohydrate, 17 % of protein and 30 % of lipids, providing 500 kcal. Blood samples 2 hours after the start of the meal were analysed for postprandial glucose (PPG) and postprandial C peptide (PCP). Fasting (M0) and postprandial beta cell responsiveness (M1) were calculated. RESULTS: The mean FPG and PPG were 7.51+/ 3.39 mmol/l and 11.02+/4.03 mmol/l respectively while the mean glycated haemoglobin (HbA1c) was 9.0+/2.5 %. The mean fasting C peptide was 1.44+/1.80ug/ml. Many of the patients (56.7 %) had low FCP levels. The mean postprandial C peptide was 4.0+/2.8 ng/ml. There were significant correlations between M1, HbA1c and PPG (p = 0.015, 0.024, 0.001 respectively) and also between M0, HbA1c, PPG and FPG (p = 0.001, 0.002, 0.001). HbA1c decreased across increasing tertiles of M0 (p < 0.001) and also M1 (p = 0.002). In step-wise linear regression analysis, M0 and M1 significantly predicted HbA1c. CONCLUSIONS: Many of the patients had low C peptide levels with poor beta cell response to the meal. The patients had poor glycaemic control and poor beta cell function. Both fasting and postprandial beta cell responsiveness were significant determinants of blood glucose and glycated haemoglobin levels. It is likely that putting these patients on insulin may have led to better glycaemic control in them.     

The Management of Hyperglycemia in Noncritically ill Hospitalized Patients Treated with Continuous Enteral or Parenteral Nutrition

Objective: Hyperglycemia is a common problem in hospitalized patients receiving artificial nutrition, and this development of hyperglycemia during parenteral nutrition therapy (PNT) and enteral nutrition therapy (ENT) increases the risks of hospital-related complications and mortality. This review aims to discuss the pathogenesis of hyperglycemia from artificial nutrition in the hospital, summarize current evidence on the treatment of hyperglycemia with insulin in these patients, and review current guidelines.Methods: A systematic literature review using PubMed and the Medical Subject Headings (MeSH) terms “hyperglycemia,” “enteral nutrition,” and “parenteral nutrition” were used to evaluate the current evidence available for treating noncritically ill patients with hyperglycemia who were receiving artificial nutrition.Results: The literature review showed that few randomized control trials exist regarding treatment of hyperglycemia in this cohort of patients, and the multiple retrospective evaluations that have addressed this topic provided varied results. In general, intravenous (IV) continuous insulin infusion offers the best glycemic control; however, this route of insulin administration is often burdensome for floor patients and their care teams. Administration of scheduled subcutaneous (SQ) insulin in patients on ENT or PNT is a safe and effective way to manage hyperglycemia, however limited data exist on an appropriate insulin regimen.Conclusion: Further prospective, randomized control trials are necessary to determine the optimal treatment of hyperglycemia for patients receiving ENT or PNT.Abbreviations: BG = blood glucose; CG = conventional glycemic control; ENT = enteral nutrition therapy; GIP = glucose-dependent insulinotropic polypeptide; GLP-1 = glucagon-like peptide 1; IG = intensive glycemic control; IV = intravenous; NPH = neutral protamine Hagedorn; PNT = parenteral nutrition therapy; SQ = subcutaneous; T2DM = type 2 diabetes mellitus; TDD = total daily dose; TPN = total parenteral nutrition     

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     

Reducing oxidative stress in patients with type 2 diabetes mellitus: A primary care call to action

Background: Oxidative stress is believed to be the primary cause of the microvascular and macrovascular complications of type 2 diabetes mellitus (DM).Objective: This paper examines the evidence linking oxidative stress with long-term complications of type 2 DM and explores methods to minimize its effect.Methods: A literature search was performed to identify relevant studies for this review. Articles published in English from 2000 to 2008 were identified through searches of PubMed, Diabetes Care, and Google using the search terms oxidative stress, postprandial hyperglycemia, ACCORD Trial, and endothelial cell dysfunction.Results: The literature search identified 423 articles. Although chronic hyperglycemia can be effectively monitored and targeted using glycosylated hemoglobin concentrations, postprandial glucose levels are also important. Postprandial glucose excursions are exhibited by almost all patients with type 2 DM and are independent risk factors for cardiovascular morbidity and mortality. Furthermore, glucose fluctuations during the postprandial period elicit more oxidative stress than chronic, sustained hyperglycemia and can lead to endothelial dysfunction, vascular inflammation, and microvascular complications. In turn, endothelial dysfunction has been implicated in the development of vascular pathologies such as atherosclerosis. Pharmacologic interventions (eg, rapid-acting insulin analogues that target post-prandial glucose excursions) reduce oxidative stress and vascular inflammation and improve endothelial dysfunction.Conclusions: Given the important role of oxidative stress in the development of complications of type 2 DM, physi-cians should consider methods to reduce oxidative stress that may occur during both acute (postprandial) and chronic hyperglycemia. One critical aspect is to reduce postprandial glucose levels to <180 mg/dL while lowering fasting glucose levels to <110 mg/dL. By coaching patients to reach these goals, physicians and other health care professionals can minimize the risk of long-term complications of type 2 DM.     

Effect of Sitagliptin on Post-Prandial Glucagon and GLP-1 Levels in Patients With Type 1 Diabetes: Investigator-Initiated,Double-Blind,Randomized, Placebo-Controlled Trial

ObjectivePeripheral insulin resistance in type 1 diabetes may be related to a paradoxical postprandial glucagon increase. This study evaluated the effects of sitagliptin (dipeptidyl peptidase-IV [DPP-IV] inhibitor, approved for patients with type 2 diabetes), in adults with type 1 diabetes to improve glycemic control through decreasing postprandial glucagon.MethodsThis investigator-initiated, double-blind, randomized-parallel 20-week study enrolled 141 subjects. Subjects received sitagliptin 100 mg/day or placebo for 16 weeks. A subset of 85 patients wore blinded continuous glucose monitors (CGM) for 5 separate 7-day periods. The primary outcome was post-meal (Boost™) reduction in 4-hour glucagon area under the curve (AUC). Secondary endpoints included changes in glycated hemoglobin (A1c), CGM data, insulin dose, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), and C-peptide levels.ResultsThere were no differences at screening between groups; however, after a 4-week run-in phase, A1c was significantly lower in the sitagliptin vs. placebo group. Post-meal GLP-1 levels were higher (P<.001) and GIP levels lower (P = .03), with glucagon suppression at 30 minutes (LS means 23.2 ± 1.9 versus 16.0 ± 1.8; P = .006) in the sitagliptin group at 16 weeks. There were no differences between the groups in change in A1c, insulin dose, weight, or C-peptide after 16 weeks of treatment. However, C-peptide positive patients randomized to sitagliplin had a non-significant trend toward decrease in A1c, mean glucose, and time spent in hyperglycemia.ConclusionSitagliptin use in type 1 diabetes did not change glucagon AUC, A1c, insulin dose, or weight despite post-meal rise in GLP-1 levels. C-peptide positive subjects treated with sitagliptin had a nonsignificant trend in decreasing hyperglycemia, which needs further evaluation. (Endocr Pract. 2013;19:19-28)     

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.     

Using Meal-Based Self-Monitoring of Blood Glucose as a Tool to Improve Outcomes in Pregnancy Complicated By Diabetes

ObjectiveTo review the importance of controlling blood glucose levels and the role of self-monitoring of blood glucose (SMBG) in the management of pregnancy complicated by diabetes.MethodsThis report describes the relationship between hyperglycemia and maternal and neonatal complications, reviews the utility of meal-based SMBG in modifying food choices and adjusting insulin doses, and proposes an algorithm to achieve normoglycemia in pregnancies complicated by diabetes.ResultsThe risk of diabetes-related complications in pregnancy is more strongly associated with 1-hour post-prandial plasma glucose concentrations than with fasting plasma glucose levels. SMBG strategies that incorporate postprandial glucose testing provide better glycemic control and greater reductions in risk of complications than does preprandial glucose testing alone. Although the optimal timing and frequency of SMBG remain controversial, available clinical evidence supports testing 4 times per day (before breakfast and 1 hour after each meal) in women with gestational diabetes managed by medical nutrition therapy only and 6 times per day (before and 1 hour after each meal) in pregnant women treated with insulin.ConclusionMeal-based SMBG is a valuable tool for improving outcomes in pregnancy complicated by diabetes. The lessons learned in this setting should have relevance to the general population of patients with diabetes, in whom microvascular and macrovascular complications are the outcomes of importance. (Endocr Pract. 2008; 14:239-247)     

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.     

Inpatient insulin therapy

Background: Many diabetic, as well as nondiabetic, hospitalized patients develop hyperglycemia. Numerous studies have demonstrated that critically ill, as well as noncritically ill, hospitalized patients who develop hyperglycemia are at increased risk for morbidity and mortality.Objective: The objective of this article was to review the risks associated with hyperglycemia in hospitalized patients, the biologic rationale for using insulin to prevent increases in glucose levels, and strategies for managing hyperglycemia in the hospital setting.Methods: We conducted a computerized search of biomedical journal literature from MEDLINE, PubMed, and Ovid published from 1994 to March 2008. We reviewed English-language original and review articles found under the subject headings “hospitalization and insulin therapy,” “inpatient diabetes and complications,” and “insulin and inflammation.”Results: More than 200 references were found during the literature search. According to the literature, the adverse outcomes that are associated with hyperglycemia may be attributed to the inflammatory and pro-oxidant effects of elevated glucose levels. The use of insulin, which has anti-inflammatory, vasodilatory, and antioxidant properties as well as the ability to inhibit lipolysis and platelet aggregation, can prevent many of these adverse outcomes.Conclusions: Hospitals should have protocols in place for using insulin to treat and prevent hyperglycemia. Subcutaneous insulin may be used for both purposes in most noncritically ill patients, whereas intravenous infusion of insulin is preferred in critically ill patients.     

Insulin requirement profiles and related factors of insulin pump therapy in patients with type 2 diabetes

Continuous subcutaneous insulin infusion(CSII) is an effective therapy to control hyperglycemia in both patients with type 1 diabetes and type 2 diabetes.However,there is little data investigating the insulin dose setting during CSII therapy in type 2 diabetes to achieve optimal glycemic control and avoid the risk of hypoglycemia.Thus,this study is aimed to assess the dose characteristics of insulin requirement and explore the related clinical factors in patients with type 2 diabetes who were treated with CSII.A total of 327 patients(195 males) aged 52.9±12.5 years old were included in this study.Patients were treated with CSII to achieve the target fasting capillary blood glucose(4.4-7.0 mmol L ~(-1)) and 2-h postprandial capillary blood glucose(4.4-10.0 mmol L ~(-1)) by adjusting insulin infusion according to the seven-point capillary blood glucose profiles.Total daily insulin dose(TDD),total daily insulin dose per kilogram(TDD kg-1) and the ratio of total basal insulin dose(TBD) to TDD(%TBa) were calculated after patients achieved the glucose targets for at least 3 days via 1-2 weeks of CSII treatment.And insulin dose,insulin dosing patterns and the relevant clinical factors were analyzed.The mean ratio of basal/bolus insulin distribution of all patients was 40%:60%.Patients with central obesity needed more TDD(51.3±17.1 U versus 43.5±14.0 U,P0.05) and TDD kg ~(-1)(0.8±0.3 U kg ~(-1) versus 0.7±0.2 U kg ~(-1),P0.05) than those without central obesity.Pearson's correlation analysis demonstrated that TDD was positively correlated with body mass index(BMI),waist circumference(WC),baseline fasting plasma glucose(FPG),fasting C-peptide level,2 h-postprandial C-peptide level and time to achieve glycemic target(all P0.05);TDD kg ~(-1) was positively correlated with waist-to-hip ratio(WHR),baseline FPG,glycosylated hemoglobin Ale(HbAlc),fasting C-peptide level and time to achieve glycemic target,and negatively correlated with BMI(all P0.05).Multiple linear regression analyses revealed that BMI(β=1.796,P0.01),WC(β=0.109,P0.01),baseline FPG(β=1.459,P0.01) and HbAlc(β=0.930,P=0.021) were independently related to TDD.Gender(β=-0.107,P=0.003),WC(β=0.005,P=0.029),baseline FPG(β=0.025,P0.01) and HbAlc(β=0.016,β=0.007) were independently associated with TDD kg ~(-1).Gender(β=-0.015,P=0.048) and disease duration(β=0.134,P=0.029) were independently associated with %TBa.%TBa is around 40% in Chinese patients with type 2 diabetes treated with CSII when glycemic control is achieved.In addition to body weight or BMI,WC and glucose levels before CSII should be considered to set TDD.Patients with central obesity or poor glycemic control might need more TDD.Higher %TBa should be considered in female patients or patients with longer disease duration.     

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.     

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.     

Efficacy and Safety of Iglarlixi in Hispanics and Non-Hispanic Whites with Type 2 Diabetes

Objective: Type 2 diabetes (T2D) is more common in Hispanic than non-Hispanic white (NHW) populations worldwide, and ethnicity, among other factors, may affect response to therapy. The efficacy and safety of insulin glargine 100 units/mL (iGlar) and the fixed-ratio combination of iGlar and the glucagon-like peptide 1 receptor agonist lixisenatide (iGlarLixi) was assessed in Hispanic and NHW patients with T2D from 25 countries.Methods: In this post hoc analysis, data from two 30-week randomized controlled trials comparing iGlar and iGlarLixi in patients with T2D uncontrolled on basal insulin ± oral antidiabetes drugs (OADs; LixiLan-L: NCT02058160) or uncontrolled on metformin ± OADs (LixiLan-O: NCT02058147) were evaluated.Results: Of the 1,512 patients included across trials, 301 were Hispanic and 1,211 NHW. Compared with iGlar, iGlarLixi resulted in greater reductions in glycated hemoglobin (A1C) and 2-hour postprandial glucose and a higher proportion of patients at target A1C <7.0% (<53 mmol/mol), regardless of ethnicity. Among NHWs from the LixiLan-L trial, documented symptomatic hypoglycemia (plasma glucose ≤70 mg/dL) rates were higher with iGlar compared with iGlarLixi (P = .06), whereas this trend was reversed among Hispanics (P = .07). Nevertheless, in both trials, a greater proportion of patients taking iGlarLixi than iGlar reached the composite efficacy endpoints of target A1C without hypoglycemia and target A1C without weight gain, regardless of ethnicity.Conclusion: These results indicate that iGlarLixi is a viable therapeutic option for both Hispanic and NHW patients with T2D, as it is efficacious without a significant increase in hypoglycemia, irrespective of ethnicity.Abbreviations: A1C = glycated hemoglobin; BMI = body mass index; FPG = fasting plasma glucose; FRC = fixed-ratio combination; GLP-1 RA = glucagon-like peptide 1 receptor agonist; HDL-C = high-density-lipoprotein cholesterol; iGlar = insulin glargine; iGlarLixi = insulin glargine + lixisenatide; LDL-C = low-density-lipoprotein cholesterol; NHW = non-Hispanic white; OAD = oral antidiabetes drug; PPG = postprandial glucose; T2D = type 2 diabetes     

Glycated Albumin at 4 Weeks Correlates with A1C Levels at 12 Weeks and Reflects Short-Term Glucose Fluctuations

Objective: Evaluate the performance of glycated albumin (GA) monitoring by comparing it to other measures of glycemic control during intensification of antidiabetic therapy.Methods: This 12-week, prospective, multicenter study compared the diagnostic clinical performance of GA to glycated hemoglobin A1C (A1C), fructosamine corrected for albumin (FRA), fasting plasma glucose (FPG), and mean blood glucose (MBG) estimated from self-monitoring of blood glucose (SMBG) and continuous glucose monitoring (CGM) in 30 patients with suboptimally controlled type 1 or 2 diabetes.Results: Mean A1C decreased from 9.5% to 8.1%. Mean SMBG correlated closely with CGM (Pearson r = 0.783 for daily estimates and r = 0.746 for weekly estimates, P<.0001). Both GA and FRA levels significantly correlated with changes from baseline in A1C and mean weekly SMBG (P<.001). The lowest observed median GA occurred at 4 weeks, followed by a small increase and then a slight reduction, mirroring changes in overall mean SMBG values. The median A1C fell throughout the treatment period, failing to reflect short-term changes in SMBG. A ≥1% reduction in GA at 4 weeks was significantly associated with a ≥0.5% change in A1C at 12 weeks (odds ratio &lsqb;OR] = 19.0, 95% confidence interval &lsqb;CI]: 1.4, 944, P = .018).Conclusion: In patients receiving glucose-lowering therapy, changes in GA at 4 weeks were concordant with changes in A1C at 12 weeks, and both GA and FRA more accurately reflected short-term blood glucose fluctuations than A1C.Abbreviations: A1C = glycated hemoglobin A1C ARIC = Atherosclerosis Risk in Communities CGM = continuous glucose monitoring FPG = fasting plasma glucose FRA = fructosamine corrected for albumin GA = glycated albumin MBG = mean blood glucose OR = odds ratio SMBG = self-monitoring of blood glucose