Type 2 diabetes mellitus (T2DM) is an expanding global health problem, closely linked to the epidemic of obesity. Individuals with T2DM are at high risk for both microvascular complications (including retinopathy, nephropathy and neuropathy) and macrovascular complications (such as cardiovascular comorbidities), owing to hyperglycaemia and individual components of the insulin resistance (metabolic) syndrome. Environmental factors (for example, obesity, an unhealthy diet and physical inactivity) and genetic factors contribute to the multiple pathophysiological disturbances that are responsible for impaired glucose homeostasis in T2DM. Insulin resistance and impaired insulin secretion remain the core defects in T2DM, but at least six other pathophysiological abnormalities contribute to the dysregulation of glucose metabolism. The multiple pathogenetic disturbances present in T2DM dictate that multiple antidiabetic agents, used in combination, will be required to maintain normoglycaemia. The treatment must not only be effective and safe but also improve the quality of life. Several novel medications are in development, but the greatest need is for agents that enhance insulin sensitivity, halt the progressive pancreatic β-cell failure that is characteristic of T2DM and prevent or reverse the microvascular complications. For an illustrated summary of this Primer, visit: http://go.nature.com/V2eGfN.

Type 2 diabetes mellitus.

Underutilization of glucose data and lack of easy and standardized glucose data collection, analysis, visualization, and guided clinical decision making are key contributors to poor glycemic control among individuals with type 1 diabetes. An expert panel of diabetes specialists, facilitated by the International Diabetes Center and sponsored by the Helmsley Charitable Trust, met in 2012 to discuss recommendations for standardization of analysis and presentation of glucose monitoring data, with the initial focus on data derived from CGM systems. The panel members were introduced to a universal software report, the Ambulatory Glucose Profile (AGP), and asked to provide feedback on its content and functionality, both as a research tool and in clinical settings. This paper provides a summary of the topics and issues discussed during the meeting and presents recommendations from the expert panel regarding the need to standardize glucose profile summary metrics and the value of a uniform glucose report to aid clinicians, researchers, and patients.

Recommendations for standardizing glucose reporting and analysis to optimize clinical decision making in diabetes: the Ambulatory Glucose Profile (AGP).

Underutilization of glucose data and lack of easy and standardized glucose data collection, analysis, visualization, and guided clinical decision making are key contributors to poor glycemic control among individuals with type 1 diabetes mellitus. An expert panel of diabetes specialists, facilitated by the International Diabetes Center and sponsored by the Helmsley Charitable Trust, met in 2012 to discuss recommendations for standardizing the analysis and presentation of glucose monitoring data, with the initial focus on data derived from continuous glucose monitoring systems. The panel members were introduced to a universal software report, the Ambulatory Glucose Profile, and asked to provide feedback on its content and functionality, both as a research tool and in clinical settings. This article provides a summary of the topics and issues discussed during the meeting and presents recommendations from the expert panel regarding the need to standardize glucose profile summary metrics and the value of a uniform glucose report to aid clinicians, researchers, and patients.

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Recommendations for Standardizing Glucose Reporting and Analysis to Optimize Clinical Decision Making in Diabetes: The Ambulatory Glucose Profile:

There is no argument that improving mean levels of glycemic control as judged by assays for glycated hemoglobin (HbA 1c ) reduces the risks of microvascular complications and cardiovascular disease events in patients with type 1 and type 2 diabetes. However, observations in some trials have suggested that targeting HbA 1c to suggested targets may not always result in improved outcomes for people with long-standing type 2 diabetes. The reasons why the glycemic control strategies that primarily use HbA 1c in these studies did not have predicted outcomes are not clear. Thus, controversy remains as to whether there are glycemic metrics beyond HbA 1c that can be defined as effective measures that can be used in addition to HbA 1c to help in assessing the risk of an individual developing diabetes complications. In this regard, the concept of “glycemic variability” (GV) is one metric that has attracted a lot of attention. GV can be simply defined as the degree to which a patient’s blood glucose level fluctuates between high (peaks) and low (nadir) levels. The best and most precise way to assess GV is also one that is still debated. Thus, while there is universal agreement that HbA 1c is the current gold standard for the primary clinical target, there is no consensus as to whether other proposed glycemic metrics hold promise to provide additional clinical data or whether there should be additional targets beyond HbA 1c . Therefore, given the current controversy, we provide a Point-Counterpoint debate on this issue. In the preceding point narrative, Dr. Hirsch provides his argument that fluctuations in blood glucose as assessed by GV metrics are deleterious and control of GV should be a primary treatment target. In the counterpoint narrative below, Dr. Bergenstal argues that there are better markers to assess the risk of diabetes than GV and provides his consideration of other concepts. —William T. Cefalu Editor in Chief, Diabetes Care

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Glycemic Variability and Diabetes Complications: Does It Matter? Simply Put, There Are Better Glycemic Markers!

OBJECTIVE To compare the effect of Roux-en-Y gastric bypass (RYGB) surgery versus intensive medical diabetes and weight management (IMWM) on clinical and patient-reported outcomes in obese patients with type 2 diabetes. RESEARCH DESIGN AND METHODS We prospectively randomized 38 obese patients with type 2 diabetes (15 male and 23 female, with mean ± SD weight 104 ± 16 kg, BMI 36.3 ± 3.4 kg/m 2 , age 52 ± 6 years, and HbA 1c 8.5 ± 1.3% [69 ± 14 mmol/mol]) to laparoscopic RYGB ( n = 19) or IMWM ( n = 19). Changes in weight, HbA 1c , cardiovascular risk factors (UKPDS risk engine), and self-reported health status (the 36-Item Short-Form [SF-36] survey, Impact of Weight on Quality of Life [IWQOL] instrument, and Problem Areas in Diabetes Survey [PAID]) were assessed. RESULTS After 3 years, the RYGB group had greater weight loss (mean −24.9 kg [95% CI −29.5, −20.4] vs. −5.2 [−10.3, −0.2]; P 1c (−1.79% [−2.38, −1.20] vs. −0.39% [−1.06, 0.28] [−19.6 mmol/mol {95% CI −26.0, −13.1} vs. −4.3 {−11.6, 3.1}]; P P P P 1c and was manifest by greater improvements in IWQOL than with either SF-36 or PAID. CONCLUSIONS Three years after randomization to RYGB versus IMWM, surgery produced greater weight loss, lower HbA 1c , reduced cardiovascular risk, and improvements in obesity-related quality of life in obese patients with type 2 diabetes.

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Clinical and Patient-Centered Outcomes in Obese Patients With Type 2 Diabetes 3 Years After Randomization to Roux-en-Y Gastric Bypass Surgery Versus Intensive Lifestyle Management: The SLIMM-T2D Study.

Context: In patients with diabetes, intraday glucose variability might predict health outcomes independently from glycosylated hemoglobin (HbA1c). Objective: Our objective was to evaluate patient satisfaction (PS), quality of life (QoL), glycemic control, and variability during insulin intensification to HbA1c below 7.0%. Patients, Design, and Setting: Eighty-two type 1 and 306 insulin-treated type 2 diabetes patients (47% male; age 54 ± 11 yr; HbA1c = 7.8 ± 0.7%) participated in this multicenter, randomized, crossover trial at 52 U.S. centers. Interventions: Interventions included insulin glargine plus premeal glulisine (n = 192) vs. twice-daily premix 75/25 or 70/30 analog insulin (n = 196) for 12 wk and crossed to the alternate arm for 12 wk. Main Outcome Measures: Main outcome measures included PS and QoL questionnaires, 3-d continuous glucose monitoring (CGM), and HbA1c every 4–8 wk. Results: Mean ± se HbA1c change was −0.39 ± 0.09% for glargine-glulisine and −0.05 ± 0.09% for premix (P < 0.0001). Th...

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Comparative effectiveness of basal-bolus versus premix analog insulin on glycemic variability and patient-centered outcomes during insulin intensification in type 1 and type 2 diabetes: a randomized, controlled, crossover trial.

Max Su

Papers

Comparative effectiveness of basal-bolus versus premix analog insulin on glycemic variability and patient-centered outcomes during insulin intensification in type 1 and type 2 diabetes: a randomized, controlled, crossover trial.