Search

Purpose: Although commonly used, HbA1c is insensitive for diagnosing prediabetes and diabetes. Glycemic variability (GV) or a 1-hour plasma glucose level (1-h PG) ≥ 155 mg/dL (8.6 mmol/L) during a 75-gram oral glucose tolerance test (OGTT) better identifies individuals with dysglycemia. The objectives were to (1) compare continuous glucose monitoring (CGM) with the OGTT for detecting dysglycemia in high-risk subjects with HbA1c < 5.7% (39 mmol/mol), and (2) correlate the 1-h PG with CGM-derived GV indices. Research Design and Methods: Subjects (n=15) with a HbA1c < 5.7% (39 mmol/mol) and at least one other risk factor for type 2 diabetes such as overweight, obesity, hypertension, or hyperlipidemia were recruited. A 2-h OGTT was performed within 3-7 days of CGM insertion, which was worn up to 14 days. Results: The average age was 50 ± 14 years, with the majority of participants being men (80%) and Caucasian (67%). The mean HbA1c was 5.3±0.2% (34 mmol/mol). The 1-h PG was highly correlated with 1-h CGM glucose levels (ρ=0.881, pConclusion: 1-h interstitial CGM glucose and 1-h PG can detect dysglycemia in high-risk subjects with HbA1c < 5.7% (39 mmol/mol). CGM may be an alternative screening tool for glucose disorders.

For over 100 years, the oral glucose tolerance test (OGTT) has been the cornerstone for detecting prediabetes and type 2 diabetes (T2DM). In recent decades, controversies have arisen identifying internationally acceptable cut points using fasting plasma glucose (FPG), 2-h post-load glucose (2-h PG), and/or HbA1c for defining intermediate hyperglycemia (prediabetes). Despite this, there has been a steadfast global consensus of the 2-h PG for defining dysglycemic states during the OGTT. This article reviews the history of the OGTT and recent advances in its application, including the glucose challenge test and mathematical modeling for determining the shape of the glucose curve. Pitfalls of the FPG, 2-h PG during the OGTT, and HbA1c are considered as well. Finally, the associations between the 30-minute and 1-hour plasma glucose (1-h PG) levels derived from the OGTT and incidence of diabetes and its complications will be reviewed. The considerable evidence base supports modifying current screening and diagnostic recommendations with the use of the 1-h PG. Measurement of the 1-h PG level could increase the likelihood of identifying high-risk individuals when the pancreatic s-cell function is substantially more intact with the added practical advantage of potentially replacing the conventional 2-h OGTT making it more acceptable in the clinical setting.

Quality Improvement Success Stories are published by the American Diabetes Association in collaboration with the American College of Physicians, Inc., and the National Diabetes Education Program. This series is intended to highlight best practices and strategies from programs and clinics that have successfully improved the quality of care for people with diabetes or related conditions. Each article in the series is reviewed and follows a standard format developed by the editors of Clinical Diabetes. The following article describes the establishment of a Diabetes Prevention Clinic for veterans with prediabetes.

Introduction: Individuals with obesity and diabetes have increased risk for atherosclerosis; contributed by chronic systemic inflammation and elevated glycemic variability (GV). Bariatric surgery reduces circulating inflammatory markers. We aimed to determine the differences in GV and the expression of inflammatory genes from circulating white blood cells (WBC) after sleeve gastrectomy (SG) in those with and without non-insulin dependent diabetes. Methods: We conducted a prospective cohort study in subjects with obesity and type 2 diabetes (n=10) and subjects with obesity and no diabetes (n=11). Research visits occurred before SG and 6 months postoperatively. Elevated GV was defined by oral glucose tolerance test derived 1-h plasma glucose ≥155 mg/dL and elevated continuous glucose monitor derived GV index-MAGE (reference range 0-2.8 mmol/l). Bulk RNA-sequencing was performed on total WBCs, isolated neutrophils, monocytes, and lymphocytes to analyze genetic expression changes in chronic 6-month weight loss from baseline. Results: At 6 months, SG caused equivalent weight loss from baseline in both groups (22%). However, HbA1c, 1-h plasma glucose, and MAGE levels were different after SG between both groups. HbA1c decreased by 3.0±1.3% in the diabetes group (p94% of total genes) were different between both groups. Furthermore, our gene set analysis showed downregulated expression of WBC genes enriched in inflammatory pathways primarily in subjects without diabetes. Conclusion: Diabetes dampens the weight-loss induced changes to transcriptomes from WBC subsets that contribute to cardiovascular disease. Elevated GV after SG may contribute to these attenuated changes.

Introduction: Sodium-glucose cotransporter-2 [SGLT2] inhibitors reduce cardiovascular events and mortality in patients with diabetes, particularly patients with established cardiovascular disease. Euglycemic diabetic ketoacidosis [euDKA], a complication of SGLT2 therapy, can be exacerbated by a low carbohydrate diet. Case Report: A 61-year-old man with a history of type 2 diabetes, taking an SGLT2 inhibitor empagliflozin 10 mg orally daily, presented to the emergency room with a 2-day history of nausea and chest pain. A week prior to presentation, he had started a ketogenic diet. He was initially admitted with a diagnosis of acute coronary syndrome. On initial assessment in the emergency room, his cardiac enzymes were normal and there were no ischemic changes in his ECG. As there was concern for unstable angina, he underwent cardiac catheterization, which showed a known total occlusion with collaterals and arteries with a non-obstructive disease without any evidence of acute plaque rupture. His baseline laboratory assessments revealed an elevated anion gap of 17, increased urinary and plasma ketones, and metabolic acidosis. His plasma glucose level was 84 mg/dL. The diagnosis of euDKA was made, and treatment with intravenous fluids and insulin was initiated. His chest pain and nausea subsequently resolved. Conclusion: We present a case of euDKA triggered by a ketogenic diet while on SGLT2 inhibitor therapy presenting as chest pain. The recognition of euDKA is important in the context of increased SGLT2 use for the management of cardiovascular risk for patients with diabetes.

For over 100 years, the oral glucose tolerance test (OGTT) has been the cornerstone for detecting prediabetes and type 2 diabetes (T2DM). In recent decades, controversies have arisen identifying internationally acceptable cut points using fasting plasma glucose (FPG), 2-h post-load glucose (2-h PG), and/or HbA1c for defining intermediate hyperglycemia (prediabetes). Despite this, there has been a steadfast global consensus of the 2-h PG for defining dysglycemic states during the OGTT. This article reviews the history of the OGTT and recent advances in its application, including the glucose challenge test and mathematical modeling for determining the shape of the glucose curve. Pitfalls of the FPG, 2-h PG during the OGTT, and HbA1c are considered as well. Finally, the associations between the 30-minute and 1-hour plasma glucose (1-h PG) levels derived from the OGTT and incidence of diabetes and its complications will be reviewed. The considerable evidence base supports modifying current screening and diagnostic recommendations with the use of the 1‐h PG. Measurement of the 1‐h PG level could increase the likelihood of identifying high-risk individuals when the pancreatic ß-cell function is substantially more intact with the added practical advantage of potentially replacing the conventional 2‐h OGTT making it more acceptable in the clinical setting.

Many health care providers screen high-risk individuals exclusively with an HbA1c despite its insensitivity for detecting dysglycemia. The 2 cases presented describe the inherent caveats of interpreting HbA1c without performing an oral glucose tolerance test (OGTT). The first case reflects the risk of overdiagnosing type 2 diabetes (T2D) in an older African American male in whom HbA1c levels, although variable, were primarily in the mid-prediabetes range (5.7-6.4% [39-46 mmol/mol]) for many years although the initial OGTT demonstrated borderline impaired fasting glucose with a fasting plasma glucose of 102 mg/dL [5.7 mmol/L]) without evidence for impaired glucose tolerance (2-hour glucose ≥140-199 mg/dl ([7.8-11.1 mmol/L]). Because subsequent HbA1c levels were diagnostic of T2D (6.5%-6.6% [48-49 mmol/mol]), a second OGTT performed was normal. The second case illustrates the risk of underdiagnosing T2D in a male with HIV having normal HbA1c levels over many years who underwent an OGTT when mild prediabetes (HbA1c = 5.7% [39 mmol/mol]) developed that was diagnostic of T2D. To avoid inadvertent mistreatment, it is therefore essential to perform an OGTT, despite its limitations, in high-risk individuals, particularly when glucose or fructosamine and HbA1c values are discordant. Innate differences in the relationship between fructosamine or fasting glucose to HbA1c are demonstrated by the glycation gap or hemoglobin glycation index.

Objective: Glycemic variability (GV) and 1 hour plasma glucose (1-h PG) ≥ 8.6 mmol/L during a 75-gram oral glucose tolerance test (OGTT) are associated with increased risk for type 2 diabetes (T2D). GV may be overlooked in high-risk individuals. The objectives of this study are: (1) to determine if continuous glucose monitoring (CGM) using the Abbott Freestyle Libre Pro can replace the OGTT in high-risk subjects with HbA1c < 5.7%; and (2) to determine if GV indices correlate with the OGTT-derived 1-h PG ≥ 8.6 mmol/L. Methods: Subjects were recruited with a HbA1c < 5.7% and at least one other risk factor including: overweight or obesity, PCOS, fatty liver, hypertension, family history of T2D, or history of gestational diabetes. The CGM, placed days prior to the OGTT, was worn up to 14 days. Anthropometric and vital signs were measured. HbA1c, fasting, 1-h and 2-h PG levels during an OGTT were obtained. Results: The 1-h PG correlated significantly with CGM glucose levels (r=0.883, p Conclusions: The 1-h CGM glucose and elevated GV indices significantly correlate with 1-h PG (> 8.6 mmol/L) in high-risk subjects with HbA1c < 5.7%. CGM could potentially replace the OGTT for detecting early dysglycemia in those with HbA1c < 5.7%. Disclosure B. Dorcely: None. E. Sifonte: None. A. Divakaran: None. K. Katz: None. R. Jagannathan: None. I.J. Goldberg: None. M. Bergman: None. Funding Abbott Diabetes Care; New York University Clinical and Translational Science Award (UL1 TR001445)

Objective Systemic inflammation contributes to cardiovascular disease in patients with type 2 diabetes, and elevated white blood cell (WBC) counts are an established risk factor. Our goal is to describe changes in WBCs and inflammatory markers after glycemic reductions in diabetes. Research design and methods This study enrolled 63 subjects with poorly controlled diabetes, defined as hemoglobin A1c (HbA1c) ≥8% [64 mmol/mol]. Circulating granulocytes and mononuclear cells were separated by histopaque double-density protocol. Inflammatory markers from these isolated WBCs were assessed at baseline and after 3 months of medical management. Results After 3 months, significant glycemic reduction, defined as a decrease in HbA1c ≥ 1.5%, occurred in 42 subjects. Fasting plasma glucose decreased by 47% (165.6 mg/dL), and HbA1c decreased from 10.2 ± 1.8 to 6.8 ± 0.9. Glycemic reductions were associated with a 9.4% decrease in total WBC counts, 10.96% decrease in neutrophils, and 21.74% decrease in monocytes. The mRNA levels of inflammatory markers from granulocytes and mononuclear cells decreased, including receptor for advanced glycation endproducts; S100 calcium binding proteins A8, A9, A12; kruppel-like factor 5; and IL-1. Also, circulating levels of IL-1β and C-reactive protein decreased. Insulin dose was a mediator between HbA1c and both total WBC and neutrophil counts, but not changes in WBC inflammatory markers. In contrast, the 17 subjects without significant glycemic reductions showed no significant differences in their WBC counts and proteins of inflammatory genes. Conclusion Significant glycemic reduction in subjects with poorly controlled diabetes led to reduced circulating WBC counts and inflammatory gene expression.

Background: Euglycemic diabetic ketoacidosis (DKA) is a known complication of sodium-glucose cotransporter 2 (SGLT2) inhibitors. We report an unusual case of euglycemic DKA caused by an SGLT2 inhibitor during self-introduction of a ketogenic diet; initial concern was for acute coronary syndrome. Clinical Case: A 61-year-old man with a history of type 2 diabetes with a hemoglobin A1c of 8.3%, coronary artery disease, hypertension, and hyperlipidemia presented to the emergency room with nausea and chest pain. The patient had a 30-year history of diabetes and was on oral therapy for years before starting insulin with an average daily dosage of 28 units. Three years ago, he started an SGLT2 inhibitor, improved his lifestyle and glycemic control, and was able to stop insulin. His home medications included empagliflozin 10 mg daily, metformin 500 mg twice a day, liraglutide 1.8 mg subcutaneously daily, rosuvastatin 5 mg daily, ezetimibe 10 mg daily, and omeprazole 40 mg daily. He reported several weeks of atypical chest pain and computed tomography angiography showed total occlusion of the mid-right coronary artery. He underwent an exercise stress test that showed echocardiographic changes that were positive for ischemia and subsequently was scheduled to undergo a left heart catheterization in 1 week. In the interim, he was highly motivated to change his lifestyle. He adopted a ketogenic diet, significantly limiting his daily carbohydrate. Five days later, he developed persistent and increased right-sided chest pain along with nausea, and presented to the emergency room. On review of systems, he reported hunger and his wife reported an odd breath odor. His vitals were stable. His troponin was negative and EKG showed inferior Q waves similar to prior EKGs. Given concern for acute coronary syndrome, he underwent cardiac catheterization, which showed the known complete total occlusion of RCA with collaterals, for which intervention was not performed. Review of additional labs showed: glucose 110 [70-100 mg/dL], bicarbonate 17 [22-29 mmol/L], anion gap 17 [6-14 mmol/L], betahydroxybutyric acid 4.1 [

Prediabetes (intermediate hyperglycemia) consists of two abnormalities, impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) detected by a standardized 75-gram oral glucose tolerance test (OGTT). Individuals with isolated IGT or combined IFG and IGT have increased risk for developing type 2 diabetes (T2D) and cardiovascular disease (CVD). Diagnosing prediabetes early and accurately is critical in order to refer high-risk individuals for intensive lifestyle modification. However, there is currently no international consensus for diagnosing prediabetes with HbA1c or glucose measurements based upon American Diabetes Association (ADA) and the World Health Organization (WHO) criteria that identify different populations at risk for progressing to diabetes. Various caveats affecting the accuracy of interpreting the HbA1c including genetics complicate this further. This review describes established methods for detecting glucose disorders based upon glucose and HbA1c parameters as well as novel approaches including the 1-hour plasma glucose (1-h PG), glucose challenge test (GCT), shape of the glucose curve, genetics, continuous glucose monitoring (CGM), measures of insulin secretion and sensitivity, metabolomics, and ancillary tools such as fructosamine, glycated albumin (GA), 1,5- anhydroglucitol (1,5-AG). Of the approaches considered, the 1-h PG has considerable potential as a biomarker for detecting glucose disorders if confirmed by additional data including health economic analysis. Whether the 1-h OGTT is superior to genetics and omics in providing greater precision for individualized treatment requires further investigation. These methods will need to demonstrate substantially superiority to simpler tools for detecting glucose disorders to justify their cost and complexity.

The number of individuals with prediabetes is expected to grow substantially and estimated to globally affect 482 million people by 2040. Therefore, effective methods for diagnosing prediabetes will be required to reduce the risk of progressing to diabetes and its complications. The current biomarkers, glycated hemoglobin (HbA1c), fructosamine, and glycated albumin have limitations including moderate sensitivity and specificity and are inaccurate in certain clinical conditions. Therefore, identification of additional biomarkers is being explored recognizing that any single biomarker will also likely have inherent limitations. Therefore, combining several biomarkers may more precisely identify those at high risk for developing prediabetes and subsequent progression to diabetes. This review describes recently identified biomarkers and their potential utility for addressing the burgeoning epidemic of dysglycemic disorders.

Identifying the earliest moment for intervention to avert progression to prediabetes and diabetes in high-risk individuals is a substantial challenge. As β-cell function is already compromised in prediabetes, attention should therefore be focused on identifying high-risk individuals earlier in the so-called pre-prediabetes stage. Biomarkers to monitor progression and identify the time point at which β-cell dysfunction occurs are therefore critically needed. Large-scale population studies have consistently shown that the 1-h plasma glucose (1-h PG) ≥ 155 mg/dl (8.6 mmol/l) during the oral glucose tolerance test detected incident type 2 diabetes and associated complications earlier than fasting plasma glucose or 2-h plasma glucose levels. An elevated 1-h PG level appears to be a better alternative to HbA1c [5.7–6.4% (37–47 mmol/mol)] or traditional glucose criteria for identifying high-risk individuals at a stage when s-cell function is substantially more intact than in prediabetes. Diagnosing high-risk individuals earlier proffers the opportunity for potentially reducing progression to diabetes, development of microvascular complications and mortality, thereby advancing benefit beyond that which has been demonstrated in global diabetes prevention programs.

Objective: The purpose of this study was to assess and compare the readability of type 2 diabetes online patient education materials from academic institutions in the northeast USA and the American Diabetes Association. Many US residents utilise the Internet to obtain health information. Studies have shown that online patient education materials are often written above the recommended fifth grade reading level, and this may pertain to diabetes health information as well. As diabetes is the seventh leading cause of death in the USA and glycaemic control is related to health literacy, the readability of diabetic health information is pertinent. Methods: Many academic institutions provide type 2 diabetes online health information. A readability analysis was conducted of materials on the websites of academic institutions or affiliate hospitals with endocrinology fellowships in the northeast USA, and from the American Diabetes Association, using 10 quantitative scales: the Flesch Reading Ease Score, the Flesch–Kincaid Grade Level, the Simple Measure of Gobbledygook, the Gunning Frequency of Gobbledygook, the New Dale–Chall Test, the Coleman–Liau Index, the New Fog Count, the Raygor Readability Estimate, the FORCAST test and the Fry Graph. Results: On average, northeast US academic institutions prepared their online diabetes patient education materials at above a 10th grade reading level. Conclusion: The readability of type 2 diabetes patient health information from academic websites is too difficult. It may benefit people with diabetes for future patient education materials to be prepared at lower reading grade levels.

Identifying the earliest time point on the prediabetic continuum is critical to avoid progressive deterioration in β-cell function. Progressively rising glucose levels even within the “normal range” occur considerably late in the evolution to diabetes thus presenting an important opportunity for earlier diagnosis, treatment, and possible reversal. An elevated 1 h postprandial glucose level, not detected by current diagnostic standards, may provide an opportunity for the early identification of those at risk. When the 1 h post-load glucose level is elevated, lifestyle intervention may have the greatest benefit for preserving β-cell function and prevent further progression to prediabetes and diabetes. In view of the considerable consistent epidemiologic data in large disparate populations supporting the predictive capacity of the1 h post-load value for predicting progression to diabetes and mortality, the time is therefore ripe to evaluate this hypothesis in a large, prospective multicenter randomized trial with lifestyle intervention.