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.     

An Update on Insulin Injection Devices

Background: Over the past 15 years, it has become clear that better glycemic control can lead to a substantial reduction in diabetic complications and that such control often requires the use of insulin therapy. However, a number of barriers exist to starting such therapy in patients with diabetes mellitus (DM). Many of these barriers to treatment are related to the use of a syringe to inject the medication. In the past ~20 years, various "pen" devices have become available that help to reduce the stigma associated with insulin injection, allowing more patients to achieve the glycemic control that they require.Objectives: This article provides an overview of the various pen devices available in the United States for subcutaneous insulin delivery and discusses the benefits these devices can provide to patients; their disadvantages are also discussed. Third-party reimbursement for these devices is highlighted.Methods: A MEDLINE search was performed (1980-2007) to identify relevant articles (English-language only) using appropriate key terms, including insulin pen and insulin delivery device. Technical specifications and availability information for the various pen devices were obtained directly from their manufacturers. Insurance coverage data were provided by major national insurance carriers.Results: There are a number of excellent pen devices available for administering each of the currently offered basal and bolus insulin analogues as well as neutral protamine Hagedorn and regular insulins. These devices range from disposable pens—which are supplied to the patient prefilled from the pharmacy, used until empty, and then discarded—to refillable digital pens, some of which have the ability to “remember” prior insulin doses. Data from various studies indicate that both patients and their physicians generally prefer insulin pens over the traditional vial and syringe delivery method. These devices are simple to use, allow patients to be more discreet in social situations, can easily be carried in a shirt pocket or purse, do not need to be refrigerated while in use, are associated with a lesser degree of injection anxiety, and may even be more accurate at lower doses. They may also be the preferred delivery system for the visually impaired, given their larger displays and the audible/tactile “click” produced each time the dose is increased by 1 U. Insulin pens lead to increased patient confidence and satisfaction and improved attitude toward insulin therapy. Most major insurance plans provide some coverage for the disposable pens as well as the cartridges for refillable pens, but this is often under tier 2 and some insurers may require prior authorization.Conclusions: Insulin pens provide DM patients with a number of advantages over a vial and syringe and can often help them overcome major barriers to the initiation of insulin therapy. The use of insulin pens leads to increased patient compliance and potential improvements in glycosylated hemoglobin, but data on glycemic control are not available. The pens should be offered to virtually all patients who require insulin therapy, except in instances in which these pens are financially prohibited.     

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.     

Common crossroads in diabetes management

The prevalence and impact of type 2 diabetes are reaching epidemic proportions in the United States. Data suggest that effective management can reduce the risk for both microvascular and macrovascular complications of diabetes. In treating patients with diabetes, physicians must be prepared not only to tailor the initial treatment to the individual and his or her disease severity but also to advance treatment as necessary and in step with disease progression. The majority of patients with diabetes are not at goal for glycated hemoglobin A1C, fasting plasma glucose, or postprandial plasma glucose levels. Although lifestyle changes based on improved diet and exercise practices are basic elements of therapy at every stage, pharmacologic therapy is usually necessary to achieve and maintain glycemic control. Oral antidiabetic agents may be effective early in the disease but, eventually, they are unable to compensate as the disease progresses. For patients unable to achieve glycemic control on 2 oral agents, current guidelines strongly urge clinicians to consider the initiation of insulin as opposed to adding a third oral agent. Recent research suggests that earlier initiation of insulin is more physiologic and may be more effective in preventing complications of diabetes. Newer, longer-lasting insulin analogs and the use of simplified treatment plans may overcome psychological resistance to insulin on the part of physicians and patients. This article summarizes the risks associated with uncontrolled fasting and postprandial hyperglycemia, briefly reviews the various treatment options currently available for type 2 diabetes, presents case vignettes to illustrate crossroads encountered when advancing treatment, and offers guidance to the osteopathic physician on the selection of appropriate treatments for the management of type 2 diabetes.     

Addition of basal insulin to oral antidiabetic agents: a goal-directed approach to type 2 diabetes therapy

The objective of this article is to review current findings in the published literature on the efficacy of insulin therapy in combination with oral antidiabetic agents, with a focus on practical information that might help to provide an evidence-based template for selecting how best to combine oral agents and basal insulin in patients with type 2 diabetes. Here we review the current oral agents used to treat type 2 diabetes, their mechanisms of action, and how they can be combined with insulin therapy to help patients achieve guideline-recommended glycemic goals. While practical advice exists for initiating a therapeutic regimen comprised of basal insulin and oral agent(s), direction as to appropriate therapy for individual patients with differing physiologic requirements is needed. Oral antidiabetic therapy in combination with insulin provides an effective therapeutic option for patients who are unable to achieve or maintain glycemic goals on oral therapy alone.     

Evolution of a pulmonary insulin delivery system (Exubera) for patients with diabetes

Many patients with diabetes fail to meet recommended glycemic goals regardless of the recognition of optimal glycemic control as a key component for improving clinical outcomes and quality of life in patients with diabetes. Patient- and physician-related barriers to the adoption of insulin therapy include fear and anxiety about injecting insulin, concerns about side effects, and personal health beliefs in regard to the use of insulin. There is an unmet need for an alternative insulin therapy that provides optimal glycemic control, is well tolerated, and improves patient adherence. Of the several inhaled insulin devices that are in various stages of development, the Exubera (INH) formulation is the first to be approved for use in the United States and in Europe. Exubera is a novel, rapid-acting inhaled human insulin formulation that has been developed for prandial insulin use. Clinical studies have shown that INH consistently improves glycemic control, in combination with longer-acting subcutaneous (SC) insulin regimens in patients with type 1 or type 2 diabetes, or is used to supplement or replace oral antidiabetic therapy in patients with type 2 diabetes. INH has demonstrated long-term safety and tolerability, with a risk for hypoglycemia similar to that of SC insulin, and no clinically meaningful changes in pulmonary function have been noted with its use. Patients treated with INH in clinical studies reported high levels of satisfaction with treatment, and many patients with diabetes choose inhaled insulin when it is offered as a treatment option. Taken together, these findings suggest that INH represents an important new development in the treatment of diabetes that may improve glycemic control in many patients with diabetes.     

Weight change in intensive insulin therapy for type 2 diabetes mellitus as a function of glycosylated hemoglobin (A1C) level achieved: The deep south diabetes program

Background: The Deep South Diabetes Program (DSDP) conducted a retrospective study to evaluate weight changes associated with intensive basal-bolus insulin therapy. Results of the effectiveness of the treatment algorithm that was used in this study were published in the April 2008 issue of Insulin.Objectives: The current study was designed to further evaluate the results of the DSDP study. The primary objective was to determine the quantitative relationship between weight gain and the patient's final glycosylated hemoglobin (A1C) level achieved. A secondary objective was to gain a qualitative understanding of the treatment parameters underlying the quantitative results.Methods: Further evaluation of the DSDP treatment algorithm in terms of weight management and A1C levels for achieving normoglycemia or near-normoglycemia was performed retrospectively using data collected in the original DSDP study. This evaluation included all patients who elected intensive basal-bolus insulin therapy and who sustained the treatment for up to 4 years. Glargine was the primary basal insulin, and aspart was the primary bolus insulin. The quantitative relationships among net weight change, net A1C change, and final A1C level achieved were evaluated. A qualitative evaluation of glycemic variability and behavioral variables was made from video recordings of patient visits during the original DSDP study and further observation of study participants after completion of the study.Results: Quantitative evaluation of change in weight as a function of A1C level achieved at the end of the study showed that for the group of patients who achieved normoglycemia, the mean change in weight was a reduction proportional to the corresponding mean reduction in A1C. For the groups of patients who did not achieve normoglycemia or near-normoglycemia, the mean change in weight was an increase proportional to the corresponding mean reduction in A1C.Conclusions: When normoglycemia was achieved and sustained using the DSDP's intensive insulin therapy, the weight gain typically seen with conventional insulin therapy did not occur. Weight gain or loss during intensive insulin therapy using the DSDP treatment algorithm was a function of A1C level achieved.     

Analysis of Effectiveness of Human U-500 Insulin in Patients Unresponsive to Conventional Insulin Therapy

ObjectiveTo present a retrospective analysis of the effects of human U-500 insulin in 20 patients with type 2 diabetes and insulin resistance.MethodsMedical records of 20 patients with type 2 diabetes who had received U-500 insulin for at least 6 months were reviewed to determine glycemic control before and after this therapy. Human regular U-500 insulin therapy was initiated at a unit dosage equivalent to the previous standard insulin dosage. Comparisons of hemoglobin A1c levels, insulin doses, and body mass index at baseline and 6 months after changing to U-500 insulin therapy were analyzed.ResultsIn the 10 female and 10 male study subjects, the mean (± SD) hemoglobin A1c level was 9.59 ± 1.37% initially, and it decreased to 8.53 ± 1.11% at 3 months and to 7.83 ± 1.26% at 6 months after initiation of U-500 insulin therapy. In comparison with baseline, these decreases were statistically significant. The amount of insulin used and the body mass index did not change significantly from baseline to 6 months after initiation of U-500 insulin treatment.ConclusionAnalysis of data suggests that U-500 insulin therapy yields improved glycemic control in insulin-resistant patients who have poor control of blood glucose with use of standard insulin regimens. There is no proof, however, that improved glycemic control by this method decreases diabetes-related complications or improves survival. Further studies must be performed before U-500 insulin can be recommended as a standard therapy for patients with insulin resistance. (Endocr Pract. 2005;11:305-307)     

Insulin resistance and diabetes in hyperthyroidism: a possible role for oxygen and nitrogen reactive species

In addition to insulin, glycemic control involves thyroid hormones. However, an excess of thyroid hormone can disturb the blood glucose equilibrium, leading to alterations of carbohydrate metabolism and, eventually, diabetes. Indeed, experimental and clinical hyperthyroidism is often accompanied by abnormal glucose tolerance. A common characteristic of hyperthyroidism and type 2 diabetes is the altered mitochondrial efficiency caused by the enhanced production of reactive oxygen and nitrogen species. It is known that an excess of thyroid hormone leads to increased oxidant production and mitochondrial oxidative damage. It can be hypothesised that these species represent the link between hyperthyroidism and development of insulin resistance and diabetes, even though direct evidence of this relationship is lacking. In this review, we examine the literature concerning the effects of insulin and thyroid hormones on glucose metabolism and discuss alterations of glucose metabolism in hyperthyroid conditions and the cellular and molecular mechanisms that may underline them.     

Sliding-Scale versus Basal-Bolus Insulin in the Management of Severe or Acute Hyperglycemia in Type 2 Diabetes Patients: A Retrospective Study

Sliding-scale and basal-bolus insulin regimens are two options available for the treatment of severe or acute hyperglycemia in type 2 diabetes mellitus patients. Although its use is not recommended, sliding-scale insulin therapy is still being used widely. The aims of the study were to compare the glycemic control achieved by using sliding-scale or basal-bolus regimens for the management of severe or acute hyperglycemia in patients with type 2 diabetes and to analyze factors associated with the types of insulin therapy used in the management of severe or acute hyperglycemia. This retrospective study was conducted using the medical records of patients with acute or severe hyperglycemia admitted to a hospital in Malaysia from January 2008 to December 2012. A total of 202 patients and 247 admissions were included. Patients treated with the basal-bolus insulin regimen attained lower fasting blood glucose (10.8±2.3 versus 11.6±3.5 mmol/L; p = 0.028) and mean glucose levels throughout severe/acute hyperglycemia (12.3±1.9 versus 12.8±2.2; p = 0.021) compared with sliding-scale insulin regimens. Diabetic ketoacidosis (p = 0.043), cardiovascular diseases (p = 0.005), acute exacerbation of bronchial asthma (p = 0.010), and the use of corticosteroids (p = 0.037) and loop diuretics (p = 0.016) were significantly associated with the type of insulin regimen used. In conclusion, type 2 diabetes patients with severe and acute hyperglycemia achieved better glycemic control with the basal-bolus regimen than with sliding-scale insulin, and factors associated with the insulin regimen used could be identified.     

pI-shifted insulin analogs with extended in vivo time action and favorable receptor selectivity

A long-acting (basal) insulin capable of delivering flat, sustained, reproducible glycemic control with once daily administration represents an improvement in the treatment paradigm for both type 1 and type 2 diabetes. Optimization of insulin pharmacodynamics is achievable through structural modification, but often at the expense of alterations in receptor affinity and selectivity. A series of isoelectric point (pI)-shifted insulin analogs based on the human insulin sequence or the GlyA21 acid stable variant were prepared by semi-synthetic methods. The pI shift was achieved through systematic addition of one or more arginine (Arg) or lysine (Lys) residues at the N terminus of the A chain, the N terminus of the B chain, the C terminus of the B chain, or through a combination of additions at two of the three sites. The analogs were evaluated for their affinity for the insulin and IGF-1 receptors, and aqueous solubility under physiological pH conditions. Notably, the presence of positively charged amino acid residues at the N terminus of the A chain was consistently associated with an enhanced insulin to IGF-1 receptor selectivity profile. Increased IGF-1 receptor affinity that results from Arg addition to the C terminus of the B chain was attenuated by cationic extension at the N terminus of the A chain. Analogs 10, 17, and 18 displayed in vitro receptor selectivity similar to that of native insulin and solubility at physiological pH that suggested the potential for extended time action. Accordingly, the in vivo pharmacokinetic and pharmacodynamic profiles of these analogs were established in a somatostatin-induced diabetic dog model. Analog 18 (A0:Arg, A21:Gly, B31:Arg, B32:Arg human insulin) exhibited a pharmacological profile comparable to that of analog 15 (insulin glargine) but with a 4.5-fold more favorable insulin:IGF-1 receptor selectivity. These results demonstrate that the selective combination of positive charge to the N terminus of the A chain and the C terminus of the B chain generates an insulin with sustained pharmacology and a near-native receptor selectivity profile.     

强化控糖后加用盐酸吡格列酮治疗2型糖尿病的临床疗效观察

目的观察强化控糖后加用盐酸吡格列酮治疗2型糖尿病的临床疗效。方法 60例使用口服降糖药物治疗的血糖控制不佳的2型糖尿病患者,入院后先进行胰岛素泵强化控糖治疗,患者血糖达到目标值后（FPG〈7.0 mmol/L,2 h PG〈10.0 mmol/L）,改为三餐前门冬胰岛素联合睡前甘精胰岛素继续强化治疗,1周后按1：1的比例随机分为两组,一组继续使用三餐前门冬胰岛素联合睡前甘精胰岛素治疗（对照组）,一组在三餐前门冬胰岛素联合睡前甘精胰岛素的基础上加用盐酸吡格列酮30 mg/日（治疗组）。1～4周我院住院治疗,5～12周门诊随访,若出现FPG及2 h PG明显下降或低血糖反应,则减少胰岛素用量。观察加用盐酸吡格列酮治疗前以及治疗12周时FPG、2 h PG、HbAlc、胰岛素用量、甘油三酯（TG）、总胆固醇（TC）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）、体重指数的变化情况。结果 （1）治疗组胰岛素用量明显下降,与加用盐酸吡格列酮治疗前有明显差异（P〈0.05）;对照组的胰岛素用量治疗前后无明显差异（P〉0.05）;（2）治疗组与对照组加用盐酸吡格列酮治疗前后FPG、2hPG均无明显差异（P〉0.05）。（3）治疗组HbAlc有所下降,与加用盐酸吡格列酮治疗前有明显差异（P〈0.05）,对照组HbAlc也有所下降,差异明显（P〈0.05）,但治疗后两组比较无明显差异（P〉0.05）。（4）加用盐酸吡格列酮后,治疗组TG下降,HDL-C升高,与同组治疗前相比,差异明显（P〈0.05）,对照组与治疗前相比差异不明显,组间比较差异有显著性（P〈0.05）。结论在强化控糖血糖达标后,加用盐酸吡格列酮继续治疗,可以明显降低患者胰岛素的使用剂量,提高患者的依从性,并且能改善血脂代谢紊乱,对于减少心血管并发症的发生有一定益处。     

Renal activity of Akt kinase in experimental Type 1 diabetes

Akt kinase regulates numerous cell functions including glucose metabolism, cell growth, survival, protein synthesis, and control of local hemodynamics. mTOR is one of down-stream effectors of Akt involved in the initiation of protein translation. However, renal Akt signaling in Type 1 diabetes (DM) in vivo, in particular under the conditions reflecting differences in metabolic control, has received less attention. Renal cortical activity and expression of Akt and mTOR (kinase assay, western blotting) were determined in streptozotocin-diabetic rats (D) with different levels of glycemic control (blood glucose 22.0+/-1.0, 13.4+/-1.5, 8.1+/-0.4 mmol/l, p<0.05 between the groups), achieved by varying insulin treatment (0, 4 and 12 IU/day), and in control rats with (C4) or without (C) chronic insulin administration. Renal Akt activity was reduced in D rats without insulin treatment and severe hyperglycemia (D-0, -62 %, p<0.01 vs. C), partially restored in moderately hyperglycemic rats (D-4, -30 %, p<0.05 vs. C), and normalized in D rats with intensive insulin and tight metabolic control (D-12). Expression of active mTOR paralleled Akt activity in D-0 (-51 %, p<0.01 vs. C), but not in D-4 and D-12 that demonstrated increases in active mTOR (+55 %, +80 % resp., p<0.05) as compared to C. Moreover, insulin activated renal Akt (+82 %, p<0.01), but not mTOR in C4. In conclusion, glycemic control and intensity of insulin treatment are important modulators of renal Akt and mTOR activity in diabetes. While Akt activity is reversible by tight metabolic control, combination of hyperglycemia and insulin treatment resulted in enhancement of mTOR activity. In addition to Akt, other signaling pathways likely contribute to regulation of renal mTOR activity in diabetes.     

Diet Is Critical for Prolonged Glycemic Control after Short-Term Insulin Treatment in High-Fat Diet-Induced Type 2 Diabetic Male Mice

Background

Clinical studies suggest that short-term insulin treatment in new-onset type 2 diabetes (T2DM) can promote prolonged glycemic control. The purpose of this study was to establish an animal model to examine such a “legacy” effect of early insulin therapy (EIT) in long-term glycemic control in new-onset T2DM. The objective of the study was to investigate the role of diet following onset of diabetes in the favorable outcomes of EIT.

Methodology

As such, C57BL6/J male mice were fed a high-fat diet (HFD) for 21 weeks to induce diabetes and then received 4 weeks of daily insulin glargine or sham subcutaneous injections. Subsequently, mice were either kept on the HFD or switched to a low-fat diet (LFD) for 4 additional weeks.

Principal Findings

Mice fed a HFD gained significant fat mass and displayed increased leptin levels, increasing insulin resistance (poor HOMA-IR) and worse glucose tolerance test (GTT) performance in comparison to mice fed a LFD, as expected. Insulin-treated diabetic mice but maintained on the HFD demonstrated even greater weight gain and insulin resistance compared to sham-treated mice. However, insulin-treated mice switched to the LFD exhibited a better HOMA-IR compared to those mice left on a HFD. Further, between the insulin-treated and sham control mice, in spite of similar HOMA-IR values, the insulin-treated mice switched to a LFD following insulin therapy did demonstrate significantly better HOMA-B% values than sham control and insulin-treated HFD mice.

Conclusion/Interpretation

Early insulin treatment in HFD-induced T2DM in C57BL6/J mice was only beneficial in animals that were switched to a LFD after insulin treatment which may explain why a similar legacy effect in humans is achieved clinically in only a portion of cases studied, emphasizing a vital role for diet adherence in diabetes control.     

The difficult choice of treatment for poorly controlled maturity onset diabetes: tablets or insulin?

Patients with maturity onset diabetes that is poorly controlled on maximal doses of oral hypoglycaemic agents are difficult to treat. A prospective randomised crossover study was performed in 58 predominantly non-obese patients on maximal doses of glibenclamide or metformin, or both, to find out if insulin would improve control or well being. The patients were given daily injections of up to 48 units of highly purified porcine lente insulin. Glycaemic control was improved by 15% or more in only 18 patients; 14 others felt better but their diabetes was no better controlled. Those whose control was improved by insulin could not be distinguished by age, duration of diabetes, body mass index, or their own treatment preference. C peptide concentrations, however, did help predict the response to insulin, the fasting C peptide to glucose ratio being considerably lower in those patients whose control was better on insulin. These findings suggest that a simple insulin regimen does not necessarily lead to better glycaemic control in maturity onset diabetes. Nevertheless, a trial of insulin is often justified since it poses few practical difficulties and makes some patients feel better even if their control is not improved. A more complex regimen might improve control in more cases, but it might also be less acceptable to older patients.     

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.     

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)     

New Digital Health Technologies for Insulin Initiation and Optimization for People With Type 2 Diabetes

ObjectiveThe health and economic burden of type 2 diabetes is of global significance. Many people with type 2 diabetes eventually need insulin to help reduce their risk of serious associated complications. However, barriers to the initiation and/or optimization of insulin expose people with diabetes to sustained hyperglycemia. In this review, we investigated how new and future technologies may provide opportunities to help overcome these barriers to the initiation and/or optimization of insulin.MethodsA focused literature search of PubMed and key scientific congresses was conducted. Software tools and devices developed to support the initiation and/or optimization of insulin were identified by manually filtering >300 publications and conference abstracts.ResultsMost software tools have been developed for smartphone platforms. At present, published data suggest that the use of these technologies is associated with equivalent or improved glycemic outcomes compared with standard care, with additional benefits such as reduced time burden and improved knowledge of diabetes among health care providers. However, there remains paucity of good-quality evidence. Most new devices to support insulin therapy help track the dose and timing of insulin.ConclusionNew digital health tools may help to reduce barriers to optimal insulin therapy. An integrated solution that connects glucose monitoring, dose recording, and titration advice as well as records comorbidities and lifestyle factors has the potential to reduce the complexity and burden of treatment and may improve adherence to titration and treatment, resulting in better outcomes for people with diabetes.     

Template to improve glycemic control without reducing adiposity or dietary fat

Drugs that improve chronic hyperglycemia independently of insulin signaling or reduction of adiposity or dietary fat intake may be highly desirable. Ad36, a human adenovirus, promotes glucose uptake in vitro independently of adiposity or proximal insulin signaling. We tested the ability of Ad36 to improve glycemic control in vivo and determined if the natural Ad36 infection in humans is associated with better glycemic control. C57BL/6J mice fed a chow diet or made diabetic with a high-fat (HF) diet were mock infected or infected with Ad36 or adenovirus Ad2 as a control for infection. Postinfection (pi), systemic glycemic control, hepatic lipid content, and cell signaling in tissues pertinent to glucose metabolism were determined. Next, sera of 1,507 adults and children were screened for Ad36 antibodies as an indicator of past natural infection. In chow-fed mice, Ad36 significantly improved glycemic control for 12 wk pi. In HF-fed mice, Ad36 improved glycemic control and hepatic steatosis up to 20 wk pi. In adipose tissue (AT), skeletal muscle (SM), and liver, Ad36 upregulated distal insulin signaling without recruiting the proximal insulin signaling. Cell signaling suggested that Ad36 increases AT and SM glucose uptake and reduces hepatic glucose release. In humans, Ad36 infection predicted better glycemic control and lower hepatic lipid content independently of age, sex, or adiposity. We conclude that Ad36 offers a novel tool to understand the pathways to improve hyperglycemia and hepatic steatosis independently of proximal insulin signaling, and despite a HF diet. This metabolic engineering by Ad36 appears relevant to humans for developing more practical and effective antidiabetic approaches.     

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.