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Technological advances have had a major effect on the management of type 1 diabetes. In addition to blood glucose meters, devices used by people with type 1 diabetes include insulin pumps, continuous glucose monitors, and, most recently, systems that combine both a pump and a monitor for algorithm-driven automation of insulin delivery. In the next 5 years, as many advances are expected in technology for the management of diabetes as there have been in the past 5 years, with improvements in continuous glucose monitoring and more available choices of systems that automate insulin delivery. Expansion of the use of technology will be needed beyond endocrinology practices to primary-care settings and broader populations of patients. Tools to support decision making will also need to be developed to help patients and health-care providers to use the output of these devices to optimise diabetes management.

Abstract Glucose and insulin metabolism in patients with diabetes are profoundly altered by advanced chronic kidney disease (CKD). Risk of hypoglycemia is increased by failure of kidney gluconeogenesis, impaired insulin clearance by the kidney, defective insulin degradation due to uremia, increased erythrocyte glucose uptake during hemodialysis, impaired counterregulatory hormone responses (cortisol, growth hormone), nutritional deprivation, and variability of exposure to oral antihyperglycemic agents and exogenous insulin. Patients with end-stage kidney disease frequently experience wide glycemic excursions, with common occurrences of both hypoglycemia and hyperglycemia. Assessment of glycemia by glycated hemoglobin (HbA1c) is hampered by a variety of CKD-associated conditions that can bias the measure either to the low or high range. Alternative glycemic biomarkers, such as glycated albumin or fructosamine, are not fully validated. Therefore, HbA1c remains the preferred glycemic biomarker despite its limitations. Based on observational data for associations with mortality and risks of hypoglycemia with intensive glycemic control regimens in advanced CKD, an HbA1c range of 7% to 8% appears to be the most favorable. Emerging data on the use of continuous glucose monitoring in this population suggest promise for more precise monitoring and treatment adjustments to permit fine-tuning of glycemic management in patients with diabetes and advanced CKD. Graphical Abstract Graphical Abstract

Abstract Context Use of continuous glucose monitoring (CGM) is increasing for insulin-requiring patients with diabetes. Although data on glycemic profiles of healthy, nondiabetic individuals exist for older sensors, assessment of glycemic metrics with new-generation CGM devices is lacking. Objective To establish reference sensor glucose ranges in healthy, nondiabetic individuals across different age groups using a current generation CGM sensor. Design Multicenter, prospective study. Setting Twelve centers within the T1D Exchange Clinic Network. Patients or Participants Nonpregnant, healthy, nondiabetic children and adults (age ≥6 years) with nonobese body mass index. Intervention Each participant wore a blinded Dexcom G6 CGM, with once-daily calibration, for up to 10 days. Main Outcome Measures CGM metrics of mean glucose, hyperglycemia, hypoglycemia, and glycemic variability. Results A total of 153 participants (age 7 to 80 years) were included in the analyses. Mean average glucose was 98 to 99 mg/dL (5.4 to 5.5 mmol/L) for all age groups except those over 60 years, in whom mean average glucose was 104 mg/dL (5.8 mmol/L). The median time between 70 to 140 mg/dL (3.9 to 7.8 mmol/L) was 96% (interquartile range, 93 to 98). Mean within-individual coefficient of variation was 17 ± 3%. Median time spent with glucose levels >140 mg/dL was 2.1% (30 min/d), and median time spent with glucose levels <70 mg/dL (3.9 mmol/L) was 1.1% (15 min/d). Conclusion By assessing across age groups in a healthy, nondiabetic population, normative sensor glucose data have been derived and will be useful as a benchmark for future research studies. This study provides normative sensor glucose data in a healthy, nondiabetic population of children and adults.

Despite substantial evidence of the benefit of frequent self-monitoring of blood glucose (SMBG) in type 1 diabetes, certain insurers limit the number of test strips that they will provide. The large database of the T1D Exchange clinic registry provided an opportunity to evaluate the relationship between the number of SMBG measurements per day and HbA1c levels across a wide age range of children and adults. The analysis included 20,555 participants in the T1D Exchange clinic registry with type 1 diabetes ≥1 year and not using a continuous glucose monitor (11,641 younger than age 18 years and 8,914 18 years old or older). General linear models were used to assess the association between the number of SMBG measurements and HbA1c levels after adjusting for potential confounding variables. A higher number of SMBG measurements per day were associated with non-Hispanic white race, insurance coverage, higher household income, and use of an insulin pump for insulin delivery (P < 0.001 for each factor). After adjusting for these factors, a higher number of SMBG measurements per day was strongly associated with a lower HbA1c level (adjusted P < 0.001), with the association being present in all age-groups and in both insulin pump and injection users. There is a strong association between higher SMBG frequency and lower HbA1c levels. It is important for insurers to consider that reducing restrictions on the number of test strips provided per month may lead to improved glycemic control for some patients with type 1 diabetes.

Proliferative retinopathy develops in a 55-year-old man with type 2 diabetes. Panretinal photocoagulation, which causes reduced production of VEGF by destroying hypoxic retinal cells, is recommended. Diminished peripheral vision and night vision can occur. Foreword This Journal feature begins with a case vignette that includes a therapeutic recommendation. A discussion of the clinical problem and the mechanism of benefit of this form of therapy follows. Major clinical studies, the clinical use of this therapy, and potential adverse effects are reviewed. Relevant formal guidelines, if they exist, are presented. The article ends with the authors' clinical recommendations. Stage A 55-year-old man with a 20-year history of type 2 diabetes mellitus was referred to a retina specialist after noticing a few black floaters in his left eye for the preceding week. His glycated hemoglobin level was 8.2%. He had no history of laser treatment for proliferative diabetic retinopathy in either eye. Ophthalmoscopic examination of the right eye showed venous beading, intraretinal microvascular abnormalities, and no macular edema. Ophthalmoscopic examination of the left eye showed extensive neovascularization of the disk, consisting of new vessels extending beyond the optic disk in all directions (Figure 1A). The retina specialist diagnosed severe . . .

Type 1 diabetes (T1D) is an autoimmune disease characterized by the destruction of insulin-producing β-cells in the pancreas. This destruction leads to chronic hyperglycemia, necessitating lifelong insulin therapy to manage blood glucose levels. Typically diagnosed in children and young adults, T1D can, however, occur at any age. Ongoing research aims to uncover the precise mechanisms underlying T1D and to develop potential interventions. These include efforts to modulate the immune system, regenerate β-cells, and create advanced insulin delivery systems. Emerging therapies, such as closed-loop insulin pumps, stem cell-derived β-cell replacement and disease-modifying therapies (DMTs), offer hope for improving the quality of life for individuals with T1D and potentially moving towards a cure. Currently, there are no disease-modifying therapies approved for stage 3 T1D. Preserving β-cell function in stage 3 T1D is associated with better clinical outcomes, including lower HbA1c and decreased risk of hypoglycemia, neuropathy, and retinopathy. Tumor Necrosis Factor alpha (TNF-α) inhibitors have demonstrated efficacy at preserving β-cell function by measurement of C-peptide in two clinical trials in people with stage 3 T1D. However, TNF-α inhibitors have yet to be evaluated in a pivotal trial for T1D. To address the promising clinical findings of TNF-α inhibitors in T1D, Breakthrough T1D convened a panel of key opinion leaders (KOLs) in the field. The workshop aimed to outline an optimal clinical path for moving TNF-α inhibitors to a pivotal clinical trial in T1D. Here, we summarize the evidence for the beneficial use of TNF-α inhibitors in T1D and considerations for strategies collectively identified to advance TNF-α inhibitors beyond phase 2 clinical studies for stage 3 T1D.

Automated insulin delivery systems that are already used in type 1 diabetes show promise for patients with type 2 diabetes, and are poised to have a substantial effect on public health.

IntroductionTo characterize glucose levels during uncomplicated pregnancies, defined as pregnancy with a hemoglobin A1c <5.7% (<39 mmol/mol) in early pregnancy, and without a large-for-gestational-age birth, hypertensive disorders of pregnancy, or gestational diabetes mellitus (ie, abnormal oral glucose tolerance test).Research design and methodsTwo sites enrolled 937 pregnant individuals aged 18 years and older prior to reaching 17 gestational weeks; 413 had an uncomplicated pregnancy (mean±SD body mass index (BMI) of 25.3±5.0 kg/m2) and wore Dexcom G6 continuous glucose monitoring (CGM) devices throughout the observed gestational period. Mealtimes were voluntarily recorded. Glycemic levels during gestation were characterized using CGM-measured glycemic metrics.ResultsParticipants wore CGM for a median of 123 days each. Glucose levels were nearly stable throughout all three trimesters in uncomplicated pregnancies. Overall mean±SD glucose during gestation was 98±7 mg/dL (5.4±0.4 mmol/L), median per cent time 63–120 mg/dL (3.5–6.7 mmol/L) was 86% (IQR: 82–89%), median per cent time <63 mg/dL (3.5 mmol/L) was 1.8%, median per cent time >120 mg/dL (6.7 mmol/L) was 11%, and median per cent time >140 mg/dL (7.8 mmol/L) was 2.5%. Mean post-prandial peak glucose was 126±22 mg/dL (7.0±1.2 mmol/L), and mean post-prandial glycemic excursion was 36±22 mg/dL (2.0±1.2 mmol/L). Higher mean glucose levels were low to moderately associated with pregnant individuals with higher BMIs (103±6 mg/dL (5.7±0.3 mmol/L) for BMI ≥30.0 kg/m2 vs 96±7 mg/dL (5.3±0.4 mmol/L) for BMI 18.5–<25 kg/m2, r=0.35).ConclusionsMean glucose levels and time 63–120 mg/dL (3.5–6.7 mmol/L) remained nearly stable throughout pregnancy and values above 140 mg/dL (7.8 mmol/L) were rare. Mean glucose levels in pregnancy trend higher as BMI increases into the overweight/obesity range. The glycemic metrics reported during uncomplicated pregnancies represent treatment targets for pregnant individuals.

IntroductionThis analysis investigated whether use of real-time continuous glucose monitoring (CGM) compared with blood glucose monitoring (BGM) results in rapidly improved glycemic management in adults with type 2 diabetes (T2D) treated with basal insulin.Research design and methodsUsing data from the MOBILE study where adults (n=175) with T2D treated with basal insulin without prandial insulin were randomized (2:1) to either CGM (n=116) or BGM (n=59), the treatment effect on glycemic management was determined over 3 months. The main outcome was a between-group difference in hemoglobin A1c (HbA1c) at 3 months adjusted for baseline value. Other outcomes included changes in CGM-derived glucose metrics and hypoglycemic events.ResultsAfter 3 months, there was a greater reduction from baseline in mean HbA1c in the CGM group compared with the BGM group, from 9.1±1.0% (76±11 mmol/mol) to 8.0±1.2% (64±13 mmol/mol) in the CGM group and from 9.0±0.9% (75±10 mmol/mol) to 8.5±1.5% (69±16 mmol/mol) in the BGM group (adjusted difference, −0.6% (95% CI –0.9% to −0.3%); −6.6 mmol/mol (95% CI –10.2 to –2.9), p<0.001). Mean time spent in range 70–180 mg/dL (3.9–10.0 mmol/L) increased significantly more in the CGM group than the BGM group (adjusted difference, +9.3% (95% CI 2.1% to 16.4%), p<0.001). There also was a greater reduction in mean time >250 mg/dL (>13.9 mmol/L) with CGM (adjusted difference, −5.8% (95% CI −10.4% to −1.2%), p<0.001) without an increase in time <70 mg/dL (<3.9 mmol/L). Mean weekly hypoglycemic event rate was lower with CGM than BGM (adjusted difference, −0.2 events per week (95% CI −0.4 to –0.1), p<0.001). Further, in the CGM group, significant improvements in CGM metrics were observed during the first 7 days of CGM use.ConclusionsIn adults with basal insulin-treated T2D, use of CGM compared with BGM resulted in rapidly improved glycemic management, with a substantial reduction in HbA1c over 3 months.Trial registration numberNCT03566693.

Abstract Context Continuous glucose monitoring (CGM) is increasingly being used both for day-to-day management in patients with diabetes and in clinical research. While data on glycemic profiles of healthy, nondiabetic individuals exist, data on nondiabetic very young children are lacking. Objective This work aimed to establish reference sensor glucose ranges in healthy, nondiabetic young children, using a current-generation CGM sensor. Methods This prospective observational study took place in an institutional practice with healthy, nondiabetic children aged 1 to 6 years with normal body mass index. A blinded Dexcom G6 Pro CGM was worn for approximately 10 days by each participant. Main outcome measures included CGM metrics of mean glucose, hyperglycemia, hypoglycemia, and glycemic variability. Results Thirty-nine participants were included in the analyses. Mean average glucose was 103 mg/dL (5.7 mmol/L). Median percentage time between 70 and 140 mg/dL (3.9-7.8 mmol/L) was 96% (interquartile range, 92%-97%), mean within-individual coefficient of variation was 17 ± 3%, median time spent with glucose levels greater than 140 mg/dL was 3.4% (49 min/day), and median time less than 70 mg/dL (3.9 mmol/L) was 0.4% (6 min/day). Conclusion Collecting normative sensor glucose data and describing glycemic measures for young children fill an important informational gap and will be useful as a benchmark for future clinical studies.