Duodenal Mucosa: A New Target for the Treatment of Type 2 Diabetes

ObjectiveAfter a high-fat and high-sugar diet, the duodenal mucosa of rodents proliferate and trigger the signal of insulin resistance, which may be the cause of type 2 diabetes (T2D). In response to this phenomenon, researchers have designed the duodenal mucosal resurfacing (DMR) procedure, mainly through the hydrothermal ablation procedure, to restore the normal mucosal surface, thereby correcting this abnormal metabolic signal. This article aims to understand the changes in duodenum before and after the onset or treatment of T2D, and the potential mechanisms of DMR procedure.MethodsA literature search of PubMed and Web of Science was conducted using appropriate keywords.ResultsBoth animal and clinical studies have shown that the villus thickness, intestinal cells, glucose transporters, enteric nerves, and gut microbiota and their metabolites in the duodenum undergo corresponding changes before and after the onset or treatment of T2D. These changes may be related to the pathogenesis of T2D. DMR procedure may produce beneficial glycemic and hepatic metabolic effects by regulating these changes.ConclusionThe duodenum is an important metabolic signaling center, and limiting nutrient exposure to this critical region will have powerful metabolic benefits. The DMR procedure may regulate glycemic and hepatic parameters through various mechanisms, which needs to be further confirmed by a large number of animal and clinical studies.     

Automated Insulin Delivery Systems as a Treatment for Type 2 Diabetes Mellitus: A Review

ObjectiveApproximately 6.3% of the worldwide population has type 2 diabetes mellitus (T2DM), and the number of people requiring insulin is increasing. Automated insulin delivery (AID) systems integrate continuous subcutaneous insulin infusion and continuous glucose monitoring with a predictive control algorithm to provide more physiologic glycemic control. Personalized glycemic targets are recommended in T2DM owing to the heterogeneity of the disease. Based on the success of hybrid closed-loop systems in improving glycemic control and safety in type 1 diabetes mellitus, there has been further interest in the use of these systems in people with T2DM.MethodsWe performed a review of AID systems with a focus on the T2DM population.ResultsIn 5 randomized controlled trials, AID systems improve time in range and reduce glycemic variability, without increasing insulin requirements or the risk of hypoglycemia.ConclusionAID systems in T2DM are safe and effective in hospitalized and closely monitored settings. Home studies of longer duration are required to assess for long-term benefit and identify target populations of benefit.     

Risk for Coexistent Autoimmune Diseases in Familial and Sporadic Type 1 Diabetes is Related to Age at Diabetes Onset

ObjectiveType 1 diabetes (T1D) is frequently associated with other autoimmune diseases (AIDs). Although most of T1D patients are sporadic cases (S-T1D), 10% to 15% have a familial form (F-T1D) involving 2 or more first-degree relatives. This study evaluated the effect of T1D family aggregation and age onset on AIDs occurrence.MethodsIn this observational, cross-sectional, case-control, single center study, we enrolled 115 F-T1D and 115 S-T1D patients matched for gender, age, T1D age onset, and duration. With respect to T1D age onset (before or after 18 years), both groups were further subdivided into young- or adult-onset F-T1D and young- or adult-onset S-T1D. The presence of organ-specific antibodies and/or overt AIDs was evaluated.ResultsThe F-T1D group had a higher percentage of AIDs (29.8% vs 18.4%, P = .04) and a significant earlier onset of AIDs at Cox regression analysis (P = .04) than the S-T1D group. Based on multivariate analysis, the adult-onset F-T1D subgroup had the highest prevalence of both additional organ-specific antibodies (60.5%) and overt AIDs (34.9%), whereas the adult S-T1D subgroup was the least frequently involved (29.1% and 12.7%, respectively). In F-T1D patients, offsprings develop T1D and AIDs earlier than their parents do.ConclusionsIn T1D patients, familial aggregation and adult-onset of T1D increase the risk for coexistent AIDs. These clinical predictors could guide clinicians to address T1D patients for the screening of T1D-related AIDs.     

Type 1 Diabetes Mellitus and Lipohypertrophy - Impact of the Intervention on Glycemic Control via Patient’s Examination and Retraining on Change of Infusion Set

ObjectiveLipohypertrophy (LH) is a common complication of insulin therapy in type 1 diabetes mellitus (T1DM). We examined whether an intervention consisting of LH assessment and retraining on insulin infusion set use improves glycemic control on subcutaneous insulin infusion (CSII) in patients with T1DM.MethodsThe intervention was conducted in 79 consecutive patients with T1DM. Data on glucose levels, glycated hemoglobin (HbA1c), and insulin doses were collected at baseline and after a median of 22 weeks (20-31.75 weeks).ResultsA total of 46 patients with T1DM (23 [50%] women) participating in the follow-up were characterized by a median age of 29 years (25-33.8 years), body mass index of 24.6 ± 3.3 kg/m², T1DM duration of 16.5 years (8.3-20 years), and subcutaneous insulin infusion duration of 7 years (4-10.8 years). Patients’ median HbA1c fell from 7.4% (6.7%-8.2%) to 7.05% (6.4%-7.6%) (P < .001), daily insulin dose/kg decreased (0.7 ± 0.20 vs 0.68 ± 0.15 IU/kg; P = .017) together with the total daily insulin dose (50.3 [40.5-62.7] vs 47.6 [39.8-62.1] IU; P = .019]. Furthermore, the percentage of basal insulin dose increased (43.0% [36-50] vs 44.0% [39.0-50.0]; P = .010], whereas the percentage of bolus dose decreased (57% [50-64] vs 56% [50-61], P = .010).ConclusionsThe structured LH-related intervention in patients with T1DM on insulin pumps resulted in better glycemic control and a decrease in total daily insulin dose.     

Nordic Walking Improves Cardiometabolic Parameters,Fitness Performance,and Quality of Life in Older Adults With Type 2 Diabetes

ObjectiveTo assess the effect of Nordic walking (NW) on cardiometabolic health, physical performance, and well-being in sedentary older adults with type 2 diabetes (T2D).MethodsFifteen subjects with T2D (female, 5; male, 10; age, 65 ± 6.2 years [mean ± standard deviation]; body mass index, 27.3 ± 4.9 kg/m² [mean ± standard deviation]) were enrolled in a 6-month NW training program. The fasting glucose and glycosylated hemoglobin levels, lipid profile (total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides), systolic blood pressure (SBP), and diastolic blood pressures were measured before and after the intervention. Participants’ quality of life (Short-Form Health Survey) and physical fitness (6-minute walking test) were also evaluated.ResultsCompared with baseline, NW significantly improved the fasting glucose level (103.5 ± 18.5 vs 168.7 ± 37.7 mg/dL, P = .01), SBP (121.8 ± 12.2 vs 133 ± 14.4 mm Hg, P = .02), physical fitness (759.88 ± 69 vs 615.5 ± 62.6 m, P < .001), and both mental health (54.5 ± 4.4 vs 45.7 ± 5.6, P < .01) and physical health (49.8 ± 4.7 vs 40.3 ± 5.9, P < .01). The levels of glycosylated hemoglobin (6.15% ± 0.8% vs 6.4% ± 1%, P = .46), total cholesterol (162.2 ± 31.2 vs 175.5 ± 28.8 mg/dL, P = .13), low-density lipoprotein cholesterol (95.2 ± 24.2 vs 106.3 ± 32.3 mg/dL, P = .43), and triglycerides (135.5 ± 60.8 vs 127.6 ± 57.4 mg/dL, P = 0.26) improved without reaching significance.ConclusionNW training improved the glycemic levels, SBP, physical fitness, and perception of quality of life in older adults with T2D. NW represents a suitable complementary strategy to improve the global health status in this population.     

Effect of Treatment of OSA With CPAP on Glycemic Control in Adults With Type 2 Diabetes: The Diabetes Sleep Treatment Trial (DSTT)

ObjectiveThe effect of obstructive sleep apnea (OSA) treatment with continuous positive airway pressure (CPAP) on glycemic measures in patients with type 2 diabetes (T2D) remains unclear. We aimed to determine whether CPAP treatment of OSA improves glycemic measures in patients with T2D.MethodsThis randomized controlled trial (N = 98) examined changes in glycemic measures following 12 weeks of active (n = 49) or sham (n = 49) CPAP and consideried participants’ adherence to CPAP therapy (percentage of days with ≥4 hours use and average hours/day of use).ResultsBaseline treatment groups were similar. Regarding the efficacy of active vs sham-CPAP over time, at 6 weeks, both groups had similar reductions in fructosamine (mean difference [MD], 95% confidence interval [CI]: CPAP ?13.10 [?25.49 to ?0.7] vs. sham ?7.26 [?20.2 to 5.69]; P = .519) but different in HbA1c (CPAP ?0.24 [?0.48 to ?0.003] vs sham 0.15 [?0.10 to 0.4]; P = .027). At 12 weeks, reductions in HbA1c values were similar by group (CPAP ?0.26 [?0.53 to 0.002] vs sham ?0.24 [?0.53 to 0.04]; P = .924). HbA1c reductions were associated with a greater percentage of cumulative days of CPAP usage ≥4 hours per day (b [SE] = 0.006 [0.002]; P = .013) and cumulative hours of CPAP use (b [SE] = 0.08 [0.08]; P = .012). CPAP use of ≥7 hours was associated with a significant reduction in HbA1c (b [SE] 0.54 [0.16]; P = .0012).ConclusionCPAP treatment of OSA did not result in sustained improved glycemic control compared to sham in the intent-to-treat analysis. CPAP adherence was associated with greater improvements in glycemic control.     

Binge-Eating Disorder and Type 2 Diabetes: A Review

ObjectiveTo familiarize health care providers with diagnosis and treatment of binge-eating disorder (BED), a common comorbidity of type 2 diabetes (T2DM).MethodsLiterature review of binge eating and T2DM. Key words used in search include BED, T2DM, obesity, and treatment.ResultsThe prevalence of BED in patients with T2DM appears to be much higher than the 2% to 3.5% prevalence seen in the general population. Studies suggest that up to 20% of patients with T2DM have an underlying eating disorder, the most common of which is binge eating. BED is probably underdiagnosed, even though there are multiple simple tools that providers can use to improve screening for the disorder. Though the relationship between BED and hemoglobin A1c control can vary, it appears that binge-eating behaviors can worsen metabolic markers, including glycemic control. Various medications used by patients with diabetes have been associated with new-onset BED, and treatment may be as simple as removing or replacing such agents. Several medications have been found to significantly reduce binge-eating frequency, and potentially, weight. Patients with BED generally benefit from psychotherapy, including cognitive behavioral therapy.ConclusionBED, only recently added to the International Classification of Disease-10 diagnostic list, is very common in patients with obesity and T2DM. The diagnosis is important to establish, as treatment or referral for treatment, could potentially improve many of the comorbidities and metrics of T2DM.     

A Clinical Prediction Model to Distinguish Maturity-Onset Diabetes of the Young From Type 1 and Type 2 Diabetes in the Chinese Population

ObjectiveGenetic detection for the diagnosis of maturity-onset diabetes of the young (MODY) in China has low sensitivity and specificity. Better gene detection is urgently needed to distinguish testing subjects. We proposed to use numerous and weighted clinical traits as key indicators for reasonable genetic testing to predict the probability of MODY in the Chinese population.MethodsWe created a prediction model based on data from 306 patients, including 140 patients with MODY, 84 patients with type 1 diabetes (T1D), and 82 patients with type 2 diabetes (T2D). This model was evaluated using receiver operating characteristic curves.ResultsCompared with patients with T1D, patients with MODY had higher C-peptide levels and negative antibodies, and most patients with MODY had a family history of diabetes. Different from T2D, MODY was characterized by lower body mass index and younger diagnostic age. A clinical prediction model was established to define the comprehensive probability of MODY by a weighted consolidation of the most distinguishing features, and the model showed excellent discrimination (areas under the curve of 0.916 in MODY vs T1D and 0.942 in MODY vs T2D). Further, high-sensitivity C-reactive protein, glycated hemoglobin A1c, 2-h postprandial glucose, and triglyceride were used as indicators for glucokinase-MODY, while triglyceride, high-sensitivity C-reactive protein, and hepatocellular adenoma were used as indicators for hepatocyte nuclear factor 1-α MODY.ConclusionWe developed a practical prediction model that could predict the probability of MODY and provide information to identify glucokinase-MODY and hepatocyte nuclear factor 1-α MODY. These results provide an advanced and more reasonable process to identify the most appropriate patients for genetic testing.     

Pragmatic Clinic-Based Investigation of Glycemic Variability in Patients With Type 1 Diabetes in Routine Clinical Practice and Its Association With Cardiovascular Autonomic Neuropathy: A Pilot Study

ObjectiveTo evaluate the relationship between markers of glycemic variability (GV), assessed by blinded continuous glucose monitoring (CGM), and cardiovascular autonomic neuropathy (CAN) in patients with type 1 diabetes (T1D).MethodsGV indices, such as SD and coefficient of variation were obtained by blinded CGM through an electrode inserted into the subcutaneous tissue for at least 3 consecutive days. CAN was assessed by cardiovascular reflex tests and HRV.ResultsFifteen T1D patients were included: 7 (46.7%) women, aged 47.1 ± 11.6 years, with a diabetes duration of 26 years (20 to 29.5 years). Five patients (25%) were excluded from our study. The majority of our patients presented glycated hemoglobin (60%), SD (86.3%), and coefficient of variation (60%) above the established goals. Patients with defined CAN had a longer diabetes duration, higher glycated hemoglobin levels, lower glomerular filtration rate, lower prevalence of indices related to hypoglycemic stress, and short-term GV indices compared with patients without CAN.ConclusionOur study showed an inverse association between GV and CAN. The most important risk factors associated with CAN were age, diabetes duration, and markers of chronic hyperglycemia. Furthermore, the difficulty in the interpretation of data extracted from the blinded CGM system, which also requires a minimum of 3 capillary blood glucose measurements for calibration, should be carefully analyzed to ensure the accuracy and usefulness of the blinded CGM system as a tool for diabetes management in developing countries. Further studies are necessary to establish the role of GV in the development of CAN in patients with T1D.     

Sequential Capecitabine/Temozolomide and Sunitinib Treatment in Patients With Metastatic Well-Differentiated Grade 1/Grade 2 Pancreatic Neuroendocrine Tumors

ObjectiveThe role of alternate sequential administration of sunitinib and capecitabine/temozolomide (CAPTEM) in metastatic pancreatic neuroendocrine tumors (PanNETs) remains unexplored. We thus aimed to analyze the efficacy and tolerability of this strategy in advanced grade 1/grade 2 PanNETs.MethodsIn total, data of 43 patients with metastatic PanNET were collected from a real-world database of a cancer center. Twenty-four patients were treated with sunitinib followed by CAPTEM (group 1), and 19 patients were treated with CAPTEM followed by sunitinib (group 2).ResultsTwenty-three patients were treated with first-line sunitinib or CAPTEM, and 20 patients were pretreated with somatostatin analog (SSA) or SSA in combination with transcatheter arterial chemoembolization. The objective response rate with first-line treatment was similar in both groups, whereas that with second-line treatment was higher in group 1 than in group 2, albeit with no significant differences (21.1% vs 5.3%, respectively; P = .205). Median progression-free survival (mPFS) for first-line and second-line treatments did not differ between the 2 groups (11 and 12 months vs 12 and 8 months, respectively). Following subgroup analyses, treatment with first-line sunitinib and sunitinib after pretreated SSA had a longer mPFS than that with second-line sunitinib after CAPTEM (11 months vs 8 months, respectively; P = .046), whereas treatment with first-line CAPTEM and CAPTEM after pretreated SSA had an mPFS similar to that of second-line CAPTEM after sunitinib treatment. CAPTEM and sunitinib had similar tolerability.ConclusionAlternating sunitinib and CAPTEM were well tolerated and associated with similar mPFS in grade 1/grade 2 PanNETs. However, larger prospective studies are required to investigate the efficacy of alternate sequential therapies for metastatic PanNET.     

Cost-Effectiveness of Empagliflozin and Metformin Combination Versus Standard Care as First-Line Therapy in Patients With Type 2 Diabetes Mellitus

ObjectiveSodium-glucose cotransporter 2 inhibitors have been shown to reduce cardiovascular events but are currently not used as the first-line therapy. This study was conducted to evaluate the cost-effectiveness of first-line empagliflozin plus metformin versus metformin monotherapy among Australians with type 2 diabetes mellitus (T2DM) and existing cardiovascular disease (CVD).MethodsA Markov model with 1-year cycles and a 5-year time horizon was constructed to simulate the occurrence of recurrent cardiovascular events among Australians aged 50 to 84 years with T2DM and CVD. Efficacy results were derived from the Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients-Removing Excess Glucose trial. Costs and utilities were drawn from published sources. The evaluation adopted both health care and societal perspectives, with the latter ascribing the Australian government’s “value of statistical life year” (A$213 000) to each year lived by a person. Future outcomes were discounted at 5% annually. Sensitivity analyses were conducted to enhance the robustness of conclusions.ResultsCompared with metformin monotherapy, first-line empagliflozin plus metformin reduced overall cardiovascular events by 0.82% and overall deaths by 7.72% over 5 years. There were 0.2 years of life saved per person and 0.16 quality-adjusted life years gained, at a net health care cost of A$4408. These equated to incremental cost-effectiveness ratios of A$22 076 per year of life saved and A$28 244 per quality-adjusted life year gained. The gains in the value of statistical life year equated to A$42 530 per person, meaning that from a societal perspective, the intervention was cost-saving.ConclusionFirst-line empagliflozin plus metformin may represent a cost-effective strategy for the management of T2DM and CVD in Australia.     

The Predictive Ability of C-Peptide in Distinguishing Type 1 Diabetes From Type 2 Diabetes: A Systematic Review and Meta-Analysis

ObjectiveThis systematic review and meta-analysis aimed to investigate the predictive ability of plasma connecting peptide (C-peptide) levels in discriminating type 1 diabetes (T1D) from type 2 diabetes (T2D) and to inform evidence-based guidelines in diabetes classification.MethodsWe conducted a holistic review and meta-analysis using PubMed, MEDLINE, EMBASE, and Scopus. The citations were screened from 1942 to 2021. The quality criteria and the preferred reporting items for systematic reviews and meta-analysis checklist were applied. The protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42022355088).ResultsA total of 23,658 abstracts were screened and 46 full texts reviewed. Of the 46 articles screened, 12 articles were included for the meta-analysis. Included studies varied by race, age, time, and proportion of individuals. The main outcome measure in all studies was C-peptide levels. A significant association was reported between C-peptide levels and the classification and diagnosis of diabetes. Furthermore, lower concentrations and the cutoff of <0.20 nmol/L for fasting or random plasma C-peptide was indicative of T1D. In addition, this meta-analysis revealed the predictive ability of C-peptide levels in discriminating T1D from T2D. Results were consistent using both fixed- and random-effect models. The I² value (98.8%) affirmed the variability in effect estimates was due to heterogeneity rather than sampling error among all selected studies.ConclusionPlasma C-peptide levels are highly associated and predictive of the accurate classification and diagnosis of diabetes types. A plasma C-peptide cutoff of ≤0.20 mmol/L is indicative of T1D and of ≥0.30 mmol/L in the fasting or random state is indicative of T2D.     

Transition From Pediatric to Adult Care for Individuals With Type 1 Diabetes: Opportunities and Challenges

ObjectivesType 1 diabetes (T1D) is a chronic disease with patients across the age spectrum that has high potential for morbidity and mortality. Unfortunately, patients transitioning from pediatric to adult care continue to demonstrate worsened glycemic control in part due to lack of understanding of transition of care best practices.MethodsThis review highlights the impact of existing transition of care interventions, assessment tools, and other recently published strategies for providers to consider to improve care of adolescent and young adult (AYA) patients with T1D in both hospital- and clinic-based settings.ResultsMany barriers impact patients with T1D during the transition period and disparities by race, sex, insurance status, and comorbid illness persist. As diabetic care continues to evolve and the prevalence of adolescents and young adults living with T1D increases, an intentional approach to transition of care is more pressing than ever. While current literature on transition of care models is limited, many show promise in improving clinic attendance and decreasing hospitalization. There are critical discussions that providers should lead with AYA patients to improve their outcomes and increase diabetes self-management, such as re-addressing carbohydrate counseling, sleep hygiene, and reproductive planning.ConclusionWhile further research on transition of care is needed, many care models offer the promise of improved T1D outcomes, enhancements in our approach to care, and increased value for our health care system at large.     

Long-Term Follow-up of Graves Orbitopathy After Treatment With Short- or Long-Term Methimazole or Radioactive Iodine

ObjectiveThe aim of this study was to compare long-term outcomes in terms of new onset or worsening of Graves orbitopathy (GO) in patients with Graves disease treated with different therapeutic modalities for hyperthyroidism.MethodsA total of 1163 patients with Graves disease were enrolled in this study; 263 patients were treated with radioiodine and 808 patients received methimazole (MMI) therapy for a median of 18 months, of whom 178 patients continued MMI for a total of 96 months (long-term methimazole [LT-MMI]). The thyroid hormonal status and GO were evaluated regularly for a median of 159 months since enrollment.ResultsThe rates of relapse, euthyroidism, and hypothyroidism at the end of follow-up were as follows: radioiodine treatment group: 16%, 22%, and 62%, respectively; short-term MMI group: 59%, 36%, and 5%, respectively; and LT-MMI group: 18%, 80%, and 2%, respectively. During the first 18 months of therapy, worsening of GO (11.5% vs 5.7%) and de novo development of GO (12.5% vs 9.8%) were significantly more frequent after radioiodine treatment (P <.004). Overall worsening and de novo development of GO from >18 to 234 months occurred in 26 (9.9%) patients in the radioiodine group and 8 (4.5%) patients in the LT-MMI group (P <.037). No case of worsening or new onset of GO was observed in patients treated with LT-MMI from >60 to 234 months of follow-up.ConclusionProgression and development of GO were associated more with radioiodine treatment than with MMI treatment; GO may appear de novo or worsen years after radioiodine treatment but not after LT-MMI therapy.     

Expert Roundtable on Continuous Glucose Monitoring

ObjectiveThe objective of this study was to define an expert opinion on continuous glucose monitoring (CGM) in persons with type 2 diabetes mellitus, including its advantages, barriers, and best clinical practices for initiation, patient-clinician communication, and data management.MethodsA series of virtual discussions was held to recommend improvements to clinical practice and design clinical tools for primary care clinicians. Participants included endocrinologists, primary care physicians, physician assistants, advanced practice nurses, and diabetes care and education specialists.ResultsThe expert panels recommended CGM as a supplement to blood glucose monitoring and hemoglobin A1c for managing diabetes in persons with diabetes (PWDs). CGM can help predict potential pitfalls in glycemic management, including hypo and hyperglycemic excursions, which directly influence lifestyle changes, medication initiation, and dosing decisions. A toolkit was designed with practical guidance on the integration of CGM into clinical practice, interpretation of results, clinical guidelines, a patient action plan, and other useful management tools.ConclusionThis review summarizes the findings from a roundtable discussion with endocrinology and primary care clinicians, a discussion of the advantages and challenges of CGM, and clinical approaches to improving the care of PWDs. CGM offers more detailed tracking of glucose levels than blood glucose monitoring or hemoglobin A1c, and it can detect asymptomatic hypoglycemia. Specialized education of providers, the cost to patients and providers, and data management are barriers to the widespread adoption of CGM for PWDs.     

Ultra Rapid-Acting Inhaled Insulin Improves Glucose Control in Patients With Type 2 Diabetes Mellitus

ObjectiveTo determine whether the use of an inhaled insulin would improve HbA1c.MethodsThis study was performed in 20 type 2 diabetes mellitus (T2DM) participants with HbA1c values ≥7.5 (58) to ≤11.5% (102 mmol/mol) on a variety of glucose-lowering regimens. Prandial Technosphere insulin (TI) was rapidly titrated based on a treatment algorithm using postprandial blood glucose to calculate premeal doses. A 2-week baseline period was followed by 12 weeks of active treatment with TI. The primary outcome was change in HbA1c. Secondary outcomes included glucose time in range (time in range: 70-180 mg/dL) obtained by a blinded continuous glucose monitoring during the baseline period and at the end of 12 weeks. Goals were to assess how to rapidly and safely initiate TI intensification, determine dosing requirements, and establish an effective dose range in uncontrolled T2DM.ResultsMean HbA1c decreased by −1.6% (−17 mmol/mol) from 9.0% (75 mmol/mol) at baseline to 7.4% (57 mmol/mol) at 12 weeks (P < .0001). Mean time in range increased from 42.2% to 65.7% (P < .0002). Mean prandial doses of TI were 18 or 19 units for all meals. Time below range was 1.1% baseline and 2.6% post treatment (P = .01).ConclusionTreatment with inhaled TI dosed using a simple algorithm improved glycemic control measured by both HbA1c and time in range, with low rates of hypoglycemia. These data add significantly to understanding TI in the management of T2DM patients for whom prandial insulin is a consideration.     

A Higher Serum Calcium Level is an Independent Risk Factor for Vision-Threatening Diabetic Retinopathy in Patients with Type 2 Diabetes: Cross-Sectional and Longitudinal Analyses

ObjectiveAn elevated serum calcium level is associated with a higher risk of type 2 diabetes (T2D), but its role in microvascular complications remains unclear. This study was conducted to investigate the association between serum calcium levels and vision-threatening diabetic retinopathy (VTDR).MethodsThis study employed a cross-sectional and longitudinal design. The cross-sectional part included all patients treated for T2D at Shanghai General Hospital between 2007 and 2016, while the longitudinal part involved an overlapping cohort of diabetic patients without VTDR who were followed from their admission until December 2019. Multivariable logistic and Cox proportional hazard regression analyses were performed, respectively. VTDR was defined as severe nonproliferative diabetic retinopathy, proliferative diabetic retinopathy, or clinically significant macular edema.ResultsA total of 3269 patients were included in the cross-sectional analysis, and 649 patients were included in the longitudinal analysis. In the cross-sectional analysis, higher corrected serum calcium (odds ratio: 1.31 per 0.1 mmol/L, 95% confidence interval: 1.16-1.49), younger age, longer diabetes duration, albuminuria, impaired renal function, and lower serum magnesium were independently associated with VTDR. In the longitudinal analysis, 95 subjects developed VTDR during follow-up (9.7 years, interquartile range: 7.4-10.9 years). Higher corrected serum calcium (hazard ratio: 1.38 per 0.1 mmol/L, 95% confidence interval: 1.10-1.72), younger age, longer diabetes duration, sub-VTDR, albuminuria, lower serum magnesium, and higher glycated hemoglobin were identified as independent risk factors for VTDR.ConclusionsA higher serum calcium level may be an independent risk factor for VTDR in patients with T2D.     

Periodontal Disease in Type 1 Diabetes Mellitus: Influence of Pubertal Stage and Glycemic Control

ObjectiveThough gingivitis is common in children with type 1 diabetes mellitus (T1DM), the overall periodontal health in T1DM during the pubertal stage is less well-characterized. The study was undertaken to explore the possible influence of puberty and metabolic derangement on periodontal health in T1DM.MethodsIn this cross-sectional study, 110 subjects between 10-18 years with T1DM and 52 healthy siblings of similar age were evaluated for pubertal stage, glycosylated hemoglobin (HbA1c), and periodontal health. Simplified oral hygiene index (OHIS), gingival index (GI), plaque index (PI), bleeding on probing (BOP), and probing depth (PPD) were evaluated at 4 sites per tooth as per 6 Ramfjord index teeth used to assess periodontal disease (PD).ResultsPD not merely gingivitis was significantly higher in T1DM (84/110, 76.36%) than the control group (28/52, 53.8%) (P = .004). Irrespective of pubertal status, children with T1DM had worse GI, PI, BOP, and PPD than nondiabetic subjects, although OHIS was better in diabetes. In both T1DM and nondiabetic subjects, pubertal subjects showed significantly worse OHIS, PPD, BOP, and GI than prepubertal subjects. PD was correlated with pubertal stage, age, and HbA1c, although less strongly with the duration of diabetes. In logistic regression, pubertal stage was a stronger predictor of PD (OR = 14.26) than age (OR = 2.22), and HbA1c (OR = 1.5) rather than the presence of diabetes and its duration.ConclusionsThough pubertal status, age, and poor glycemic control rather than the presence of diabetes and its duration are associated with gingivitis and other forms of PD, puberty had a more profound effect in the pathogenesis of PD in T1DM.