A scalable application of Artificial Intelligence-Driven Insulin Titration Program to transform Type 2 Diabetes Management.

BACKGROUND: Despite new pharmacotherapy, most patients with long-term Type 2 Diabetes are still hyperglycemic. This could have been solved by insulin with its unlimited potential efficacy, but its dynamic physiology demands frequent titrations which are overdemanding. This report provides a real-life account for a scalable transformation of diabetes care in a community-based endocrinology center by harnessing AI-based autonomous insulin titration. METHODS: The center embedded the d-Nav® technology and its dedicated clinical support. Reported outcomes include treatment efficacy/safety in the first 600 patients and use of cardiorenal-risk reduction pharmacotherapy. FINDINGS: Patients used d-Nav for 8.2±3.0 months with 82% retention. Age was 67.1±11.5 years and duration of diabetes was 19.8±11.0 years. During the last 3 years before d-Nav, HbA1c had been overall higher than 8% and at the beginning of the program it was as high as 8.6%±2.1% with 29.3% of the patients with HbA1c>9%. With d-Nav, HbA1c decreased to 7.3%±1.2% with 5.7% of patients with HbA1c>9%. During the first 3 months, d-Nav reduced total daily dose of insulin in 1 of every 5 patients due to relatively low glucose levels to minimize the risk of hypoglycemia. GLP-1 or dual GLP-1 and GIP receptor agonists were prescribed in about a half of the patients and SGLT2 inhibitor in a third. The frequency of hypoglycemia (<54mg/dl) was 0.4±0.6/month and severe hypoglycemia 1.7/100-patient-years. INTERPRETATION: The use of d-Nav allowed for improvement in overall diabetes management with appropriate use of both insulin and non-insulin pharmacologic agents in a scalable way.

Challenging the 50-50 rule for the basal-bolus insulin ratio in patients with type 2 diabetes who maintain stable glycaemic control.

BACKGROUND: For patients using basal-bolus insulin therapy, it is widespread clinical practice to aim for a 50-50 ratio between basal and total daily bolus. However, this practice was based on a small study of individuals without diabetes. To assess the rule in real-world practice, we retrospectively analyzed patients on basal-bolus therapy that was adjusted at least weekly by an artificial intelligence-driven titration within the d-Nav® Insulin Management Technology. MATERIALS AND METHODS: We obtained de-identified data from the Diabetes Centre of Ulster Hospital for patients with four inclusion criteria: type 2 Diabetes (T2D), on d-Nav >6 months, on basal-bolus insulin therapy >80% of the time (based on insulin analogs), and no gap in data >3 months. RESULTS: We assembled a cohort of 306 patients, followed by the d-Nav service for 3.4 ± 1.8 years (mean ± SD), corresponding to about 180 autonomous insulin dose titrations and about 5000 autonomous individual dose recommendations per patient. After an initial run-in period, mean glycated hemoglobin (HbA1c) values in the cohort were maintained close to 7%. Surprisingly, in just over three-quarters of the cohort, the average basal insulin fraction was <50%; in half of the cohort average basal insulin fraction <41.2%; and in one-quarter the basal insulin fraction was <33.6%. Further, the basal insulin fraction did not remain static over time. In half of the patients, the basal insulin fraction varied by ≥1.9×; and, in 25% of the patients, ≥2.5×. CONCLUSION: Our data show that a 50-50 ratio of basal-to-bolus insulin does not generally apply to patients with T2D who successfully maintain stable glycemia. Therefore, the 50-50 ratio should not serve as an ongoing treatment guide. Moreover, our results emphasize the importance of at least weekly insulin titrations.

For debate; pharmacological priorities in advanced type 2 diabetes.

A multitude of therapeutic agents have been available to treat patients with Type 2 diabetes. Unfortunately, many patients with advanced Type 2 diabetes continue to suffer from complications and premature death. To date, all available guidelines emphasize a variety of therapeutic aspects, goals, and pharmacological combinations, without directing the clinician as to which is a higher priority. The following review attempts to clarify which therapeutic option is more important for prognosis in patients with advanced type 2 diabetes. The body of evidence presented, reveal that the most important marker for prognosis is HbA1c. Each 1% incrementally higher HbA1c than ~7% is associated with 15%-45% reduced survival rates. Therefore, any agents that can achieve the time-sensitive objective of lowering HbA1c levels should be used.

Automated insulin dosing guidance to optimise insulin management in patients with type 2 diabetes: a multicentre, randomised controlled trial.

BACKGROUND: Insulin therapy is most effective if dosage titrations are done regularly and frequently, which is seldom practical for most clinicians, resulting in an insulin titration gap. The d-Nav Insulin Guidance System (Hygieia, Livonia, MI, USA) is a handheld device that is used to measure glucose, determine glucose patterns, and automatically determine the appropriate next insulin dose. We aimed to determine whether the combination of the d-Nav device and health-care professional support is superior to health-care professional support alone. METHODS: In this multicentre, randomised, controlled study, we recruited patients from three diabetes centres in the USA (in Detroit MI; Minneapolis, MN; and Des Moines IA). Patients were eligible if they were aged 21-70 years, diagnosed with type 2 diabetes with a glycated haemoglobin (HbA1c) concentration of 7·5% or higher (≥58 mmol/mol) and 11% or lower (≤97 mmol/mol), and had been using the same insulin regimen for the previous 3 months. Exclusion criteria included body-mass index of 45 kg/m2 or higher; severe cardiac, hepatic, or renal impairment; and more than two severe hypoglycaemic events in the past year. Eligible participants were randomly assigned (1:1), with randomisation blocked within each site, to either d-Nav and health-care professional support (intervention group) or health-care professional support alone (control group). Both groups were contacted seven times (three face-to-face and four phone visits) during 6 months of follow-up. The primary objective was to compare average change in HbA1c from baseline to 6 months. Safety was assessed by the frequency of hypoglycaemic events. The primary objective and safety were assessed in the intention-to-treat population. We used Student's t test to assess the primary outcome for statistical significance. This study was registered with ClinicalTrials.gov, number NCT02424500. FINDINGS: Between Feb 2, 2015, and March 17, 2017, 236 patients were screened for eligibility, of whom 181 (77%) were enrolled and randomly assigned to the intervention (n=93) and control (n=88) groups. At baseline, mean HbA1c was 8·7% (SD 0·8; 72 mmol/mol [SD 8·8]) in the intervention group and 8·5% (SD 0·8; 69 mmol/mol [SD 8·8]) in the control group. The mean decrease in HbA1c from baseline to 6 months was 1·0% (SD 1·0; 11 mmol/mol [SD 11]) in the intervention group, and 0·3% (SD 0·9; 3·3 mmol/mol [9·9]) in the control group (p<0·0001). The frequency of hypoglycaemic events per month was similar between the groups (0·29 events per month [SD 0·48] in the intervention group vs 0·29 [SD 1·12] in the control group; p=0·96). INTERPRETATION: The combination of automated insulin titration guidance with support from health-care professionals offers superior glycaemic control compared with support from health-care professionals alone. Such a solution facilitated safe and effective insulin titration in a large group of patients with type 2 diabetes, and now needs to be evaluated across large health-care systems to confirm these findings and study cost-effectiveness. FUNDING: US National Institutes of Health, National Institute of Digestive and Kidney Diseases.

THE EFFICACY AND SAFETY OF CO-ADMINISTRATION OF SITAGLIPTIN WITH METFORMIN IN PATIENTS WITH TYPE 2 DIABETES AT HOSPITAL DISCHARGE.

OBJECTIVE: Few randomized controlled trials have focused on the optimal management of patients with type 2 diabetes (T2D) during the transition from the inpatient to outpatient setting. This multicenter open-label study explored a discharge strategy based on admission hemoglobin A1c (HbA1c) to guide therapy in general medicine and surgery patients with T2D. METHODS: Patients with HbA1c ≤7% (53 mmol/mol) were discharged on sitagliptin and metformin; patients with HbA1c between 7 and 9% (53-75 mmol/mol) and those >9% (75 mmol/mol) were discharged on sitagliptinmetformin with glargine U-100 at 50% or 80% of the hospital daily dose. The primary outcome was change in HbA1c at 3 and 6 months after discharge. RESULTS: Mean HbA1c on admission for the entire cohort (N = 253) was 8.70 ± 2.3% and decreased to 7.30 ± 1.5% and 7.30 ± 1.7% at 3 and 6 months ( P<.001). Patients with HbA1c <7% went from 6.3 ± 0.5% to 6.3 ± 0.80% and 6.2 ± 1.0% at 3 and 6 months. Patients with HbA1c between 7 and 9% had a reduction from 8.0 ± 0.6% to 7.3 ± 1.1% and 7.3 ± 1.3%, and those with HbA1c >9% from 11.3 ± 1.7% to 8.0 ± 1.8% and 8.0 ± 2.0% at 3 and 6 months after discharge (both P<.001). Clinically significant hypoglycemia (<54 mg/dL) was observed in 4%, 4%, and 7% among patients with a HbA1c <7%, 7 to 9%, and >9%, while a glucose <40 mg/dL was reported in <1% in all groups. CONCLUSION: The proposed HbA1c-based hospital discharge algorithm using a combination of sitagliptin-metformin was safe and significantly improved glycemic control after hospital discharge in general medicine and surgery patients with T2D. ABBREVIATIONS: BG = blood glucose; DPP-4 = dipeptidyl peptidase-4; eGFR = estimated glomerular filtration rate; HbA1c = hemoglobin A1c; T2D = type 2 diabetes.

Insulin therapy, weight gain and prognosis.

Insulin therapy is mainly used by people with type 2 diabetes who have failed other therapies and have become insulin-deficient. This group represents about a quarter of all people with type 2 diabetes. Almost all those with type 2 diabetes who start insulin therapy or intensify it gain weight, which may potentially diminish the prognostic advantage of improved glycaemia. To date, all available guidelines emphasize both the attainment of glycated haemoglobin (HbA1c) goals and weight control, without directing the clinician as to which element is of a higher priority. The following review attempts to clarify the issue using the available literature. The body of evidence presented in this review indicates that glycaemic management with exogenous insulin replacement is of a much higher priority than weight gain. Lower weight or weight loss do not show prognostic benefit in advanced stages of diabetes; therefore, weight gain should not discourage providers from achieving and maintaining HbA1c goals with insulin therapy, regardless of insulin dosage or other medications.

Temporary Reductions in Insulin Requirements Are Associated with Hypoglycemia in Type 2 Diabetes.

Background: In patients with type 2 diabetes, insulin therapy necessitates regular and frequent dosage titration to overcome variations in insulin requirements. The goal of this study was to evaluate changes in insulin requirements, using data from a technology-based insulin-titration service. Methods: To keep glycemia stable, the service adjusts and records insulin dosage at least weekly. Therefore, insulin dosage closely tracks insulin requirement. Events of considerable and persistent decrease in insulin requirements were identified by reductions in total daily dose (TDD) of insulin ≥25%. Periods ended when a persistent increase in TDD of insulin has started. The average frequency of hypoglycemia was expressed as any glucose reading <54 mg/dL (both inside or outside periods of decrease in insulin dosage) divided by the total number of months for each patient. Results: Patients (n = 246) were followed for 2.8 ± 0.9 years. Reductions of TDD of insulin were experienced by 70.3% of the patients, occurred 0.8 ± 0.5 times per year, lasted 10.0 ± 7.7 weeks, and insulin requirements declined by 39.9% ± 12.6%. The frequency of hypoglycemia (<54 mg/dL) was low, at 0.5 ± 0.6 per month, and the difference in frequencies in biphasic/premixed and basal-bolus insulin regimens was not statistically significant. Hypoglycemia was 6.5 times more prevalent during reductions in TDD of insulin. Conclusions: Sizeable changes in insulin requirements occur over time, which demand persistent and frequent titration to preserve treatment safety.

Type 2 diabetes specialty clinic model for the accountable care organization era.

AIMS: A third of the patients with Type 2 diabetes have an advance disease that requires complex pharmacotherapies and advanced expertise, dependent on multiple clinical interactions. Unfortunately, limited providers availability enables only sporadic interactions. Additionally, the expanding Accountable Care Organization (ACO) concept enhances providers' compensation when clinical performance is improving while limiting face-to-face clinic visits. METHODS: We developed an advanced type 2 specialty clinic model, geared toward frequent remote clinical interventions while limiting face-to-face clinic visits. The model was tested in a 1-year, prospective, randomized controlled clinical trial. N=60, patients were randomized 1:1, to the experimental or standard endocrinology clinics. RESULTS: Average A1c in the experimental arm decreased from 9.6±0.9% to 7.9±1.3%(p<0.0001). Whereas in the control it decreased from 8.9±0.8% to 8.6±1.9%(non-significant). More patients were treated with statins in the experimental arm compared to the control (93.3% vs. 66.7%; p=0.01). Face-to-face clinic visits occurred 1.5±0.7 times per year in the experimental arm compared to 3.6±4.0 in the control (p<0.0001). CONCLUSIONS: We believe that the presented model for a modified type 2 diabetes specialty clinic may enhance providers accessibility and patients' outcomes while improving reimbursement in the ACO model.

Efficacy of sitagliptin for the hospital management of general medicine and surgery patients with type 2 diabetes (Sita-Hospital): a multicentre, prospective, open-label, non-inferiority randomised trial.

BACKGROUND: The role of incretin-based drugs in the treatment of patients with type 2 diabetes admitted to hospital has not been extensively assessed. In this study, we compared the safety and efficacy of a dipeptidyl peptidase-4 inhibitor (sitagliptin) plus basal insulin with a basal-bolus insulin regimen for the management of patients with type 2 diabetes in general medicine and surgery in hospitals. METHODS: We did a multicentre, prospective, open-label, non-inferiority randomised clinical trial (Sita-Hospital) in five hospitals in the USA, enrolling patients aged 18-80 years with type 2 diabetes and a random blood glucose concentration of 7·8-22·2 mmol/L who were being treated with diet or oral antidiabetic drugs or had a total daily insulin dose of 0·6 units per kg or less, admitted to general medicine and surgery services. We randomly assigned patients (1:1) to receive either sitagliptin plus basal glargine once daily (the sitagliptin-basal group) or a basal-bolus regimen with glargine once daily and rapid-acting insulin lispro or aspart before meals (the basal-bolus group) during the hospital stay. All other antidiabetic drugs were discontinued on admission. The randomisation was achieved by computer-generated tables with block stratification according to randomisation blood glucose concentrations (ie, higher or lower than 11·1 mmol/L). The primary endpoint of the trial was non-inferiority in mean differences between groups in their daily blood glucose concentrations during the first 10 days of therapy (point-of-care measurements; non-inferiority was deemed a difference <1 mmol/L). The safety endpoints included hypoglycaemia and uncontrolled hyperglycaemia leading to treatment failure. All participants who received at least one dose of study drug were included in the analysis. This study is registered with ClinicalTrials.gov, number NCT01845831. FINDINGS: Between Aug 23, 2013, and July 27, 2015, we recruited 279 patients, and randomly assigned 277 to treatment; 138 to sitagliptin-basal and 139 to basal-bolus. The length of stay in hospital was similar for both groups (median 4 days [IQR 3-8] vs 4 [3-8] days, p=0·54). The mean daily blood glucose concentration in the sitagliptin-basal group (9·5 mmol/L [SD 2·7]) was not inferior to that in the basal-bolus group 9·4 mmol/L [2·7]) with a mean blood glucose difference of 0·1 mmol/L (95% CI -0·6 to 0·7). No deaths occurred in this trial. Treatment failure occurred in 22 patients (16%) in the sitagliptin-basal group versus 26 (19%) in the basal-bolus group (p=0·54). Hypoglycaemia occurred in 13 patients (9%) in the sitagliptin-basal group and in 17 (12%) in the basal-bolus group (p=0·45). No differences in hospital complications were noted between groups. Seven patients (5%) developed acute kidney injury in the sitagliptin-basal group and six (4%) in the basal-bolus group. One patient (0·7%) developed acute pancreatitis (in the basal-bolus group). INTERPRETATION: The trial met the non-inferiority threshold for the primary endpoint, because there was no significant difference between groups in mean daily blood glucose concentrations. Treatment with sitagliptin plus basal insulin is as effective and safe as, and a convenient alternative to, the labour-intensive basal-bolus insulin regimen for the management of hyperglycaemia in patients with type 2 diabetes admitted to general medicine and surgery services in hospital in the non-intensive-care setting. FUNDING: Merck.

Adrenal Lymphangioma Masquerading as a Catecholamine Producing Tumor.

Objective. To report the unusual case of an adrenal lymphangioma presenting in a patient with an adrenal cystic lesion and biochemical testing concerning for pheochromocytoma. The pertinent diagnostic and imaging features of adrenal lymphangiomas are reviewed. Methods. We describe a 59-year-old patient who presented with hyperhidrosis and a 2.2 by 2.2 cm left adrenal nodule. Biochemical evaluation revealed elevated plasma-free normetanephrine, urine normetanephrine, urine vanillylmandelic acid, and urine norepinephrine levels. Elevated plasma norepinephrine levels were not suppressed appropriately with clonidine administration. Results. Given persistent concern for pheochromocytoma, the patient underwent adrenalectomy. The final pathology was consistent with adrenal lymphangioma. Conclusions. Lymphangiomas are benign vascular lesions that can very rarely occur in the adrenal gland. Imaging findings are generally consistent with a cyst but are nonspecific. Excluding malignancy in patients presenting with adrenal cysts can be difficult. Despite its benign nature, the diagnosis of adrenal lymphangioma may ultimately require pathology.

A novel approach to optimise glycaemic control in insulin users.

Insulin therapy has been available for almost a century. However, its success rate is still disappointing where the majority of users sustain harmfully elevated glycated haemoglobin (HbA1c) levels. The key element essential for effective and safe insulin therapy is frequent dosage titration to overcome constant variations in insulin requirements. In reality, dosage titration is done sporadically during clinic visits. A scalable solution to this problem is being reviewed. A diabetes nurses service improves glycaemic control without overburdening the health system. The service relies on a handheld device, which provides patients with an insulin dose recommendation for each injection while using the device to monitor glucose. Similar to the approach providers use during clinical encounters, the device analyses stored glucose trends and constantly titrates insulin dosage without care providers' supervision. In this report, we describe the logic behind the technology by providing examples from users.

Insulin therapy for pre-hyperglycemic beta-cell endoplasmic reticulum crowding.

Insulin therapy improves ß-cell function in early stages of diabetes by mechanisms that may exceed alleviation of glucotoxicity. In advance type 2 diabetes, hyperglycemia causes ß-cell damage and ultimately ß-cell loss. At such an advanced stage, therapeutic modalities are often inadequate. Growing evidence indicates that in early stages of type-2 diabetes and some types of monogenic diabetes linked with malfunctioning endoplasmic-reticulum (ER), the ß-cell ER fails to process sufficient proinsulin once it becomes overloaded. These changes manifest with ER distention (ER-crowding) and deficiency of secretory granules. We hypothesize that insulin therapy may improves ß-cell function by alleviating ER-crowding. To support this hypothesis, we investigated pre-diabetic ß-cell changes in hProC(A7)Y-CpepGFP transgenic mice that develop prolonged pre-diabetes due to proinsulin dysmaturation and ER-crowding. We attenuated the ß-cell ER proinsulin synthesis with a treat-to-target insulin therapy while avoiding hypoglycemia and weight gain. Alleviation of ER-crowding resulted in temporary improvement in proinsulin maturation, insulin secretion and glucose tolerance. Our observations suggest that alleviation of pre-diabetic ER-crowding using a treat-to-target insulin therapy may improve ß-cell function and may prevent further metabolic deterioration.

Can a tool that automates insulin titration be a key to diabetes management?

BACKGROUND: Most patients who use insulin do not achieve optimal glycemic control and become susceptible to complications. Numerous clinical trials have shown that frequent insulin dosage titration is imperative to achieve glycemic control. Unfortunately, implementation of such a paradigm is often impractical. We hypothesized that the Diabetes Insulin Guidance System (DIGS™) (Hygieia, Inc., Ann Arbor, MI) software, which automatically advises patients on adjustment of insulin dosage, would provide safe and effective weekly insulin dosage adjustments. SUBJECTS AND METHODS: In a feasibility study we enrolled patients with type 1 and type 2 diabetes, treated with a variety of insulin regimens and having suboptimal glycemic control. The 12-week intervention period followed a 4-week baseline run-in period. During the intervention, DIGS processed patients' glucose readings and provided insulin dosage adjustments on a weekly basis. If approved by the study team, the adjusted insulin dosage was communicated to the patients. Insulin formulations were not changed during the study. The primary outcome was the fraction of DIGS dosage adjustments approved by the study team, and the secondary outcome was improved glycemic control. RESULTS: Forty-six patients were recruited, and eight withdrew. The DIGS software recommended 1,734 insulin dosage adjustments, of which 1,731 (99.83%) were approved. During the run-in period the weekly average glucose was stable at 174.2±36.7 mg/dL (9.7±2.0 mmol/L). During the following 12 weeks, DIGS dosage adjustments resulted in progressive improvement in average glucose to 163.3±35.1 mg/dL (9.1±1.9 mmol/L) (P<0.03). Mean glycosylated hemoglobin decreased from 8.4±0.8% to 7.9±0.9% (P<0.05). Concomitantly, the frequency of hypoglycemia decreased by 25.2%. CONCLUSIONS: The DIGS software provided patients with safe and effective weekly insulin dosage adjustments. Widespread implementation of DIGS may improve the outcome and reduce the cost of implementing effective insulin therapy.

Frequent insulin dosage adjustments based on glucose readings alone are sufficient for a safe and effective therapy.

PROBLEM: Frequent dosage adjustments are necessary to achieve effective insulin therapy. However, a controversy surrounds the pertinent clinical parameters required to make effective and safe insulin titrations. We hypothesize that glucose readings are sufficient to adjust insulin dosage provided that it is done on a weekly basis. METHODS: In a prospective pilot study, we recruited 14 subjects with suboptimally controlled insulin-treated Type-2 and Type-1 diabetes. Subjects were treated with basal-bolus insulin therapy that was titrated weekly for 12 weeks. Dosage adjustments were made by the study Endocrinologist by reviewing subjects' glucose readings, exclusively based on logsheets and contingent upon the approval of the on-site study team. To corroborate that the glucose readings were sufficient for making dosage adjustments, we used software to process only glucose readings and recommend insulin dosage adjustments. The recommendations made by the software were retrospectively compared to the ones made by the study Endocrinologist. RESULTS: All N=568 recommendations were approved by the study team and in 99.3% of the cases the recommendations were clinically similar to the ones made by the software. No hazardous disagreements were found. The mean A1C improved from 9.8% (± 2.0) to 7.9% (± 1.3) (p=0.001) in 12 weeks and the weekly mean glucose progressively improved from 220.3 mg/dl (± 51.9) to 151.5 mg/dl (± 19.2) (p<0.0001). The frequency of minor hypoglycemia was 22.7 per patient-year in subjects with Type-2 diabetes and 42.7 in the subjects with Type-1 diabetes. No severe hypoglycemic events occurred. CONCLUSIONS: Glucose readings are sufficient to adjust insulin therapy in a safe and effective manner, when adjustments are made on a weekly basis. Thus, dedicated software may help adjust insulin dosage between clinic visits.

In vivo misfolding of proinsulin below the threshold of frank diabetes.

OBJECTIVE: Endoplasmic reticulum (ER) stress has been described in pancreatic ß-cells after onset of diabetes-a situation in which failing ß-cells have exhausted available compensatory mechanisms. Herein we have compared two mouse models expressing equally small amounts of transgenic proinsulin in pancreatic ß-cells. RESEARCH DESIGN AND METHODS: In hProCpepGFP mice, human proinsulin (tagged with green fluorescent protein [GFP] within the connecting [C]-peptide) is folded in the ER, exported, converted to human insulin, and secreted. In hProC(A7)Y-CpepGFP mice, misfolding of transgenic mutant proinsulin causes its retention in the ER. Analysis of neonatal pancreas in both transgenic animals shows each ß-cell stained positively for endogenous insulin and transgenic protein. RESULTS: At this transgene expression level, most male hProC(A7)Y-CpepGFP mice do not develop frank diabetes, yet the misfolded proinsulin perturbs insulin production from endogenous proinsulin and activates ER stress response. In nondiabetic adult hProC(A7)Y-CpepGFP males, all ß-cells continue to abundantly express transgene mRNA. Remarkably, however, a subset of ß-cells in each islet becomes largely devoid of endogenous insulin, with some of these cells accumulating large quantities of misfolded mutant proinsulin, whereas another subset of ß-cells has much less accumulated misfolded mutant proinsulin, with some of these cells containing abundant endogenous insulin. CONCLUSIONS: The results indicate a source of pancreatic compensation before the development of diabetes caused by proinsulin misfolding with ER stress, i.e., the existence of an important subset of ß-cells with relatively limited accumulation of misfolded proinsulin protein and maintenance of endogenous insulin production. Generation and maintenance of such a subset of ß-cells may have implications in the avoidance of type 2 diabetes.

The effort required to achieve and maintain optimal glycemic control.

BACKGROUND: Insulin therapy is most effective when dosage is frequently adjusted. We sought to evaluate the effort required to maintain A1C below 7% once attained in older patients with type 2 diabetes. METHODS: A total of 2380 insulin dosage adjustment episodes were analyzed for their intensity and frequency. The data were divided into an "induction period" (n=608), defined as the time before subjects' A1C dropped below 7% for the first time, and a "maintenance period" (n=1772), defined as the remaining study period. The data originated from a published study and included 26 older subjects with suboptimally controlled type 2 diabetes treated for a year with intensive insulin therapy. To achieve therapy goals, the study team contacted the subjects once every few weeks, reviewed records and optimized the insulin dosage. RESULTS: During both the induction and maintenance periods, insulin dosage (both long-acting and fast-acting) was adjusted by more than 20%. Maintaining A1C below 7% required dosage adjustments every 2.7(±1.0) weeks, averaging 11.4% (±4.0) in 2.0 (±0.3) different components of insulin dosage (i.e., two of either long-acting or short-acting for breakfast, lunch or dinner) per contact. CONCLUSIONS: Considerable effort was required to maintain optimal A1C levels in older patients with type 2 diabetes. Since the full benefit of insulin therapy is attained only when multiple components of insulin dosage are frequently adjusted and given the growing shortage of care providers' availability, innovative approaches are needed to empower patients to safely make their own insulin adjustments.