Characteristics of adult- compared to childhood-onset type 1 diabetes.

AIMS: To compare diagnosis characteristics, diabetes management and comorbidities in a population diagnosed with type 1 diabetes in childhood with those in a similar population diagnosed in adulthood to identify disease differences related to the age of diabetes onset. METHODS: This analysis was performed using the T1D Exchange Clinic Registry, a cross-sectional survivor cohort. Retrospectively collected characteristics were compared across the following age-at-diagnosis groups: <10, 10-17, 18-24, 25-39 and ≥40 years. RESULTS: The entire cohort included 20 660 participants [51% female, median (interquartile range) age 18 (14-36) years, 82% non-Hispanic white]. Diabetic ketoacidosis at diagnosis was more common among those with onset in childhood. Participants diagnosed as adults were more likely to be overweight/obese at diagnosis and to have used oral agents preceding type 1 diabetes diagnosis (57%). Current insulin pump use was less frequent in participants diagnosed at older ages. Current glycaemic control, measured by HbA1c , insulin requirements and use of a continuous glucose monitor were not different by age at diagnosis. Coeliac disease was the only comorbidity that was observed to have a different frequency by age at diagnosis, being more common in the participants diagnosed at a younger age. CONCLUSIONS: These results show differences and similarities between type 1 diabetes diagnosed in childhood vs adulthood; notably, there was a tendency for there was a higher frequency of diabetic ketoacidosis at onset in children and a higher frequency of use of oral antidiabetes agents in adults. The data indicate that there is little distinction between the clinical characteristics and outcomes of type 1 diabetes diagnosed in childhood vs adulthood. Optimizing glycaemic control remains a challenge in all age groups, with lower use of insulin pumps impacting those diagnosed as adults.

Associations between HbA1c and continuous glucose monitoring-derived glycaemic variables.

AIMS: To identify clinically useful associations between HbA1c levels and various continuous glucose monitoring-derived metrics. METHODS: We retrospectively analysed end-of-study HbA1c levels and >2 weeks of continuous glucose monitoring data collected from 530 adults with Type 1 diabetes or insulin-requiring Type 2 diabetes during four randomized trials. Each trial lasted ≥24 weeks and provided central laboratory end-of-study HbA1c levels and continuous glucose monitoring data from the preceding 3 months. Participants were assigned to groups based on either HbA1c levels or continuous glucose monitoring-derived glucose values. RESULTS: HbA1c was strongly correlated with mean glucose value (r=0.80), time spent with glucose values in the 3.9-10.0 mmol/l range (time in range; r=-0.75) and percentage of glucose values >13.9 mmol/l (r=0.72), but was weakly correlated with the percentage of glucose values <3.9 mmol/l (r=-0.39) or <3.0 mmol/l (r=-0.21). The median percentage of glucose values <3.0 mmol/l was <1.2% (<20 min/day) for all HbA1c -based groups, but the median percentage of values >13.9 mmol/l varied from 2.5% (0.6 h/day) to 27.8% (6.7 h/day) in the lowest and highest HbA1c groups, respectively. More than 90% of participants with either <2% of glucose values >13.9 mmol/l, mean glucose <7.8 mmol/l, or time in range >80% had HbA1c levels ≤53 mmol/mol (≤7.0%). For participants with HbA1c ≥64 mmol/mol (≥8.0%), the median time in range was 44%, with 90% of participants having a time in range of <59%. CONCLUSIONS: The associations shown in the present study suggest that continuous glucose monitoring-derived metrics may help guide diabetes therapy intensification efforts in an HbA1c -independent manner.

Effect of liraglutide on anthropometric measurements, sagittal abdominal diameter and adiponectin levels in people with type 2 diabetes treated with multiple daily insulin injections: evaluations from a randomized trial (MDI-liraglutide study 5).

AIM: Use of the glucagon-like peptide 1 receptor agonist liraglutide has been shown to reduce weight. Different types of anthropometric measurements can be used to measure adiposity. This study evaluated the effect of liraglutide on sagittal abdominal diameter, waist circumference, waist-to-hip ratio and adiponectin levels in people with type 2 diabetes (T2D) treated with multiple daily insulin injections (MDI). MATERIALS AND METHODS: In the multicentre, double-blind, placebo-controlled MDI-liraglutide trial, 124 individuals with T2D treated with MDI were randomized to either liraglutide or placebo. Basal values of weight, waist circumference, waist-to-hip ratio, sagittal abdominal diameter and adiponectin were compared with measurements at 12 and 24 weeks after randomization. RESULTS: Baseline-adjusted mean weight loss was 3.8 ± 2.9 kg greater in liraglutide than placebo-treated individuals (p < 0.0001). Waist circumference was reduced by 2.9 ± 4.3 cm and 0.2 ± 3.6 cm in the liraglutide and placebo groups, respectively, after 24 weeks (baseline-adjusted mean difference: 2.6 ± 4.0 cm, p = 0.0005). Corresponding reductions in sagittal abdominal diameter were 1.1 ± 1.7 cm and 0.0 ± 1.8 cm (baseline-adjusted mean difference: 1.1 ± 1.7 cm, p = 0.0008). Hip circumference was reduced in patients randomized to liraglutide (baseline-adjusted mean difference between treatment groups: 2.8 ± 3.8 cm, p = 0.0001), but there was no significant difference between the groups in either waist-to-hip ratio (baseline-adjusted mean difference: 0.0 ± 0.04 cm, p = 0.51) or adiponectin levels (baseline-adjusted mean difference: 0.8 ± 3.3 mg L-1, p = 0.17). Lower HbA1c and mean glucose levels measured by masked continuous glucose monitoring at baseline were associated with greater effects of liraglutide on reductions in waist circumference and sagittal abdominal diameter. CONCLUSIONS: In patients with T2D, adding liraglutide to MDI may reduce abdominal and hip obesity to a similar extent, suggesting an effect on both visceral and subcutaneous fat. Liraglutide had greater effects on reducing abdominal obesity in patients with less pronounced long-term hyperglycaemia but did not affect adiponectin levels.

Non-insulin treatments for Type 1 diabetes: critical appraisal of the available evidence and insight into future directions.

Intensive insulin therapy is the mainstay of treatment for people with Type 1 diabetes, but hypoglycaemia and weight gain are often limiting factors in achieving glycaemic targets and decreasing the risk of diabetes-related complications. The inclusion of pharmacological agents used traditionally in Type 2 diabetes as adjuncts to insulin therapy in Type 1 diabetes has been explored, with the goal of mitigating such drawbacks. Pramlintide and metformin result in modest HbA1c and weight reductions, but their use is limited by poor tolerability and, in the case of pramlintide, by frequency of injections and cost. The addition of glucagon-like peptide-1 receptor agonists to insulin results in improved glycaemic control, reduced insulin doses and weight loss, but this is at the expense of higher rates of hypoglycaemia and hyperglycaemia with ketosis. Sodium-glucose co-transporter-2 and dual sodium-glucose co-transporter-2 and -1 inhibitors also improve glucose control, but with reductions in weight and insulin requirements potentiating the risk of acidosis-related events and hypoglycaemia. The high proportion of people with Type 1 diabetes not achieving glycaemic targets, the negative clinical impact of intensive insulin therapy and the rise in obesity and cardiovascular disease and mortality, underline the need for individualized clinical care. The evaluation of new therapies, effective in Type 2 diabetes, as adjuncts to insulin therapy represents a promising strategy, particularly given the beneficial effects on cardiovascular and renal outcomes in people with Type 2 diabetes with or at high risk of complications that are also observed in patients with Type 1 diabetes. As the population with Type 1 diabetes ages, our mission is to evolve and provide better tools and improved therapies to excel, not only in glycaemic control but also in risk reduction and reduction of complications.

Safety and efficacy of insulin degludec/insulin aspart with bolus mealtime insulin aspart compared with standard basal-bolus treatment in people with Type 1 diabetes: 1-year results from a randomized clinical trial (BOOST® T1).

AIMS: To evaluate the long-term safety and efficacy of a simplified basal-bolus regimen of once-daily insulin degludec/insulin aspart (IDegAsp) with additional IAsp vs. a standard basal-bolus insulin regimen of insulin detemir (IDet) with IAsp in adults with Type 1 diabetes. METHODS: This was an open-label trial comprising a 26-week core phase followed by a 26-week extension phase. Participants were randomized to IDegAsp once daily at the main meal and IAsp at remaining meals (IDegAsp+IAsp), or IDet (once or twice daily) and IAsp at all meals (IDet+IAsp). Insulins were titrated to target plasma glucose of < 5 mmol/l (< 90 mg/dl) at pre-breakfast (IDegAsp and IDet) and at pre-meal (IAsp). RESULTS: After 52 weeks, the overall confirmed hypoglycaemia rate was 31.8 episodes/patient-years of exposure (PYE) with IDegAsp+Asp and 36.7 episodes/PYE with IDet+IAsp, and the rate of nocturnal confirmed hypoglycaemia was significantly lower with IDegAsp+Asp than with IDet+IAsp (3.1 vs. 5.4 episodes/PYE, respectively; P < 0.05). Adverse event rates were comparable between groups. Mean HbA1c decreased from baseline by 0.7% (IDegAsp+IAsp) and 0.6% (IDet+IAsp), achieving 60 or 61 mmol/mol (7.6% or 7.7%, respectively), at Week 52. The mean total daily insulin dose was lower with IDegAsp+IAsp than with IDet+IAsp (ratio: 0.87; 95% CI 0.79-0.95; P = 0.0026). CONCLUSIONS: Once-daily treatment with IDegAsp and IAsp as bolus insulin for remaining meals was associated with significantly lower risk of nocturnal confirmed hypoglycaemia, improved glycaemic control and showed non-inferiority compared with IDet+IAsp, the standard of care in Type 1 diabetes.

Blood glucose control using a computer-guided glucose management system in allogeneic hematopoietic cell transplant recipients.

Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative treatment for patients with hematological malignancies. However, is associated with substantial rates of morbidity and mortality. We and others have shown that malglycemia is associated with adverse transplant outcome. Therefore, improving glycemic control may improve transplant outcome. In this prospective study we evaluated the feasibility of using Glucommander (a Computer-Guided Glucose Management System; CGGM) in order to achieve improved glucose control in hospitalized HCT patients. Nineteen adult patients contributed 21 separate instances on CGGM. Patients were on CGGM for a median of 43 h. Median initial blood glucose (BG) on CGGM was 244 mg/dL, and patients on 20 study instances reached the study BG target of 100-140 mg/dL after a median of 6 h. After BG reached the target range, the median average BG level per patient was 124 mg/dL. Six patients had a total of 10 events of BG <70 mg/dL (0.9% of BG measurements), and no patients experienced BG level <40 mg/dL. The total estimated duration of BG <70 mg/dL was 3 h (0.2% of the total CGGM time). In conclusion, our study demonstrates that stringent BG control in HCT patients using CGGM is feasible.

Options for prandial glucose management in type 2 diabetes patients using basal insulin: addition of a short-acting GLP-1 analogue versus progression to basal-bolus therapy.

Integrating patient-centered diabetes care and algorithmic medicine poses particular challenges when optimized basal insulin fails to maintain glycaemic control in patients with type 2 diabetes. Multiple entwined physiological, psychosocial and systems barriers to insulin adherence are not easily studied and are not adequately considered in most treatment algorithms. Moreover, the limited number of alternatives to add-on prandial insulin therapy has hindered shared decision-making, a central feature of patient-centered care. This article considers how the addition of a glucagon-like peptide 1 (GLP-1) analogue to basal insulin may provide new opportunities at this stage of treatment, especially for patients concerned about weight gain and risk of hypoglycaemia. A flexible framework for patient-clinician discussions is presented to encourage development of decision-support tools applicable to both specialty and primary care practice.

Self-monitoring of blood glucose.

Many would argue that the introduction of modern-day diabetes management started 30 years ago with the introduction of self-monitoring of blood glucose (SMBG) at home. While that may be true, it is interesting that many of today's fundamental questions have yet to be answered. Furthermore, the technology itself continues to change, to improve and to better exist with our non-diabetes technology. For example, the first SMBG 'apps' are available now for smart-phones (iPhone), and we can expect the phones themselves to participate more directly with SMBG and diabetes management. Still, both researchers (and payors) continue to ask some fundamental questions. 1. What is the efficacy of SMBG for patients not requiring insulin therapy? 2. What is the optimum frequency of SMBG for patients who do require insulin therapy? 3. What is the role of software to assist in data management for SMBG (for both patients and clinicians)? 4. What is the cost effectiveness of SMBG for all of the different patient populations with diabetes? 5. What is the ideal chemistry which results in the least amount of interfering substances with SMBG? 6. What is an acceptable accuracy for SMBG both at home and in the hospital? The accuracy question is more important than ever since all continuous glucose monitoring (CGM) for now are calibrated with SMBG results. 7 What is the best strategy for teaching patients how best to use their SMBG data? 8. What is the best way to integrate SMBG with insulin pump therapy? 9. What is the role of SMBG with today's CGM devices? 10. What will the role of SMBG be 5-10 years from now with future CGM devices? These are just some of the questions which need more thought and study as we move into 2011. In this chapter we have selected papers that appeared in the PubMed on this topic and chose those we thought were most influential in this area. We have then addressed many of these topics although answers are far from clear for many of them. Although SMBG is not 'new' technology, much research needs to be completed before we fully understand this tool's full impact, particularly as CGM becomes more popular.

Sulphonylurea-metformin combination therapy, cardiovascular disease and all-cause mortality: the Fremantle Diabetes Study.

AIM: To determine whether combination of metformin-sulphonylurea is associated with an increased risk of cardiovascular disease (CVD) and mortality in an urban community-based cohort of type 2 patients. METHODS: We studied 1271 (98.2%) of 1294 type 2 participants in the observational Fremantle Diabetes Study (mean age 64.2 years, 48.8% males) who had detailed diabetes-specific therapy recorded at baseline and complete follow-up data. Mortality and hospital discharge data were collected over 13 174 patient-years (mean +/- SD: 10.4 +/- 3.9 years). Cox proportional hazards modelling was used to determine whether baseline diabetes treatments were independently associated with cardiovascular mortality, hospitalization for/death from CVD or all-cause mortality after adjustment for other explanatory variables. RESULTS: During follow-up, 523 deaths occurred (41.1%) of which 269 (51.4%) were attributed to CVD. Hospitalization for CVD as principal diagnosis occurred at least once for 481 (37.8%) participants. In Kaplan-Meier analyses, there were significant differences in cardiovascular mortality, hospitalization for/death from CVD and all-cause mortality between diabetes therapy groups (p < 0.001). Compared with diet and metformin monotherapy, those treated with metformin-sulphonylurea had higher cardiovascular and all-cause mortality (p < or = 0.024). Insulin users had significantly higher cardiovascular mortality, hospitalization for/death from CVD and all-cause mortality than those on combination therapy (p < or = 0.016). After adjustment for significant variables in the most parsimonious models, diabetes treatment was not independently associated with any of the three study endpoints (p > or = 0.49). CONCLUSIONS: Combination metformin-sulphonylurea appears as safe as other blood glucose-lowering therapies used for type 2 diabetes.

Self-monitoring of blood glucose.

Studies have shown that reducing A1c levels can delay and/or reduce the overall risk of microvascular and macrovascular complications associated with both type 1 and type 2 diabetes (1-5). Implementation of intensive diabetes management [using insulin pumps or multiple daily injections along with increased frequency of self-monitoring of blood glucose (SMBG)] is expensive although there is a significant reduction in risk of long-term complications and cost (6,7). Although the benefits of optimal glucose control seem clear, the risk of severe hypoglycaemia can be a barrier to achieving this goal (1,4,5). In fact, there is nearly a threefold increase in hypoglycaemia with intensification of treatment in type 1 diabetes (1). This is further complicated by the results of recent clinical trials in type 2 diabetes [ACCORD (8), ADVANCE (9) and VADT (10)]. The results of these trials have shown conflicting outcomes in the intensively treated arm. This paradox has created a need for new technology that will facilitate optimal glucose control by recommending appropriate insulin doses while decreasing the risk of hypoglycaemia. There is no doubt of the role of SMBG in insulin-requiring patients with diabetes as it helps guide patients and the providers to adjust their insulin dose on a daily basis. There is enough data documenting the beneficial effects of increased SMBG in such individuals. However, the story for patients with type 2 diabetes not on insulin therapy is different. There is no consensus on frequency and timing of SMBG and its exact impact on glucose control in non-insulin-requiring individuals with type 2 diabetes is debatable. Part of the reason for this controversy may be related to increasing healthcare cost and thus payers finding ways not to reimburse SMBG, since there is conflicting data and the evidence of SMBG improving long-term outcomes in such individuals is not fully evaluated. The prevalence of diabetes is rising worldwide and there are more than 24 million people, with both type 1 and 2 diabetes (diagnosed and undiagnosed), in the USA (11-15). With a limited number of endocrinologists or diabetes specialists available in the USA, most clinical diabetes care is provided by primary care physicians (16). Tools to help patients adjust their insulin dose at home should help in improving their glucose control. Several technologies such as continuous glucose monitors (sensors) and glucometers (SMBG) are on the market and have been shown to help patients improve glucose excursions, reduce glucose variability, decrease time spent in hypoglycaemia and hyperglycaemia and improve A1c levels (17-19). Other software available on insulin pumps can also guide patients with adjustment of insulin dose, especially meal-time boluses (20). We hope that the future might see many such technologies being used on a regular basis to guide providers and patients for better long-term outcomes.

Hyperglycemic crises in diabetes mellitus type 2.

Hyperglycemic crises in type 2 diabetes are not rare and are becoming increasingly recognized as part of the spectrum of the presentation of previously undiagnosed diabetes mellitus and the decompensation of established diabetes mellitus. Contributing factors and associations are being elucidated but remain far from clear, particularly in DKA states. Medications commonly used in the treatment of many comorbid illnesses in patients with diabetes can themselves predispose to HHS. Endocrinopathies can contribute to insulin resistance and directly increase the glycemic load, leading to hyperglycemia. Medications such as the protease inhibitors may in the future lead to a better understanding of the pathophysiology of the metabolic derangements seen in the development of type 2 diabetes mellitus.

Islet cell antibodies and glutamic acid decarboxylase antibodies, but not the clinical phenotype, help to identify type 1(1/2) diabetes in patients presenting with type 2 diabetes.

This study was undertaken to determine which type 1 diabetes-associated autoantibodies and what clinical characteristics are most useful to identify patients with type 1(1/2) diabetes. We studied 125 patients, recently diagnosed clinically with type 2 diabetes for the presence of islet cell antibodies (ICA), insulin autoantibodies (IAA), antibodies to glutamic acid decarboxylase(GADAb), and IA-2a (IA-2Ab). Patients with a diagnosis of type 2 diabetes who met all of the following criteria at diagnosis were studied: age > or = 30 years, no history of ketonuria or ketoacidosis, and not requiring insulin treatment. Thirty-six patients (29%) were positive for at least 1 antibody. Thirty-two (26%) were ICA positive and 20 (16%) GADAb positive. Insulin autoantibodies and IA-2Ab occurred less frequently in 2 (1.6%) and 8 (6.4%) patients, respectively. There was no significant difference in the ages at diagnosis between the Ab(+) and Ab(-) patients, age in years (range) 47.2 (32 to 64) versus 51.2 (31 to 77), respectively, P =.06. Body mass index (BMI) was different in the 2 groups, with Ab(+) patients being less obese, BMI (range) 28.3 kg/m(2) (17.6 to 54.9) versus 32.0 kg/m(2) (19.2 to 68.8), respectively, P =.01. Clinical presentation of diabetes was more commonly symptomatic with polyuria and polydipsia in Ab(+) patients, while in Ab(-) patients, diagnosis was more often incidental, P =.002. However, more than 95% of patients overlapped in both age and BMI irrespective of antibody status. Similarly, 42% of Ab(+) patients had their diabetes diagnosed incidentally, while 29% of Ab(-) patients presented with polyuria and polydipsia. We therefore conclude that screening with antibodies, mainly ICA and GAD, but not age, BMI, or clinical presentation should be used to identify type 1(1/2) diabetes.

Improving the quality of outpatient care for older patients with diabetes: lessons from a comparison of rural and urban communities.

OBJECTIVE: Our goal was to compare the quality of diabetic care received by patients in rural and urban communities. STUDY DESIGN: We performed a retrospective analysis of claims data captured by the Medicare program. POPULATION: We included all fee-for-service Medicare patients 65 years and older living in the state of Washington who had 2 or more physician encounters for diabetes care during 1994. OUTCOME MEASURES: The outcomes were the extent to which patients received 3 specific recommended services: glycated hemoglobin determination, cholesterol measurement, and eye examination. RESULTS: A total of 30,589 Medicare patients (8.4%) were considered to have diabetes; 29.1% lived in rural communities. Generalists provided most diabetic care in all locations. Patients living in small rural towns received almost half their outpatient care in larger communities. Patients living in large rural towns remote from metropolitan areas were more likely to have received the recommended tests than patients in all other groups. Patients who saw an endocrinologist at least once during the year were more likely to have received the recommended tests. CONCLUSIONS: Large rural towns may provide the best conditions for high-quality care: They are vibrant, rapidly growing communities that serve as regional referral centers and have an adequate-but not excessive-supply of both generalist and specialist physicians. Generalists provide most diabetic care in all settings, and consultation with an endocrinologist may improve adherence to guidelines.

Less hypoglycemia with insulin glargine in intensive insulin therapy for type 1 diabetes. U.S. Study Group of Insulin Glargine in Type 1 Diabetes.

OBJECTIVE: Insulin glargine (21A-Gly-30Ba-L-Arg-30Bb-L-Arg-human insulin) is a biosynthetic insulin analog with a prolonged duration of action compared with NPH human insulin. This study compared insulin glargine with NPH human insulin in subjects with type 1 diabetes who had been previously treated with multiple daily injections of NPH insulin and regular insulin. RESEARCH DESIGN AND METHODS: This study was a multicenter randomized parallel-group study in which subjects were randomized to receive premeal regular insulin and either insulin glargine (at bedtime) or NPH insulin (at bedtime for patients on once-daily therapy and at bedtime and in the morning for patients on twice-daily therapy) for up to 28 weeks. Dose titration of both basal insulins was based on capillary fasting whole blood glucose (FBG) levels; the goal was a premeal blood glucose concentration of 4.4-6.7 mmol/l. RESULTS: A total of 534 well-controlled type 1 diabetic subjects (mean GHb 7.7%, mean fasting plasma glucose [FPG] 11.8 mmo/l) were treated. A small decrease in GHb levels was noted with both insulin glargine (-0.16%) and NPH insulin (-0.21%; P > 0.05). Significant reductions in median FPG levels from baseline (-1.67 vs. -0.33 mmol/l with NPH insulin, P = 0.0145) and a trend for a reduction in capillary FBG levels were achieved with insulin glargine. After the 1-month titration phase, significantly fewer subjects receiving insulin glargine experienced symptomatic hypoglycemia (39.9 vs. 49.2%, P = 0.0219) or nocturnal hypoglycemia (18.2 vs. 27.1%, P = 0.0116) with a blood glucose level <2.0 mmol/l compared with subjects receiving NPH insulin. CONCLUSIONS: Lower FPG levels with fewer episodes of hypoglycemia were achieved with insulin glargine compared with once- or twice-daily NPH insulin as part of a basal-bolus regimen in patients with type 1 diabetes.

Nonhypoglycemic drug reactions of agents used to treat diabetes.

The different classes of agents now available for the treatment of diabetes, each with its own unique mechanism of action, present the clinician with numerous choices to achieve glycemic control. Therapy can be tailored for each patient. If the primary problem is insulin resistance, a thiazolidinedione can be used. The clinician should remember the potential adverse reactions of the drugs and their potential interaction with other conditions a patient may have. After this careful consideration, the optimal therapeutic regimen for a patient can be developed.

Type 1 diabetes mellitus and the use of flexible insulin regimens.

The management of type 1 diabetes mellitus (formerly known as insulin-dependent diabetes) has changed dramatically over the past 30 years. In particular, new insulin strategies have improved the ability to maintain near-normal glycemia. Factors such as onset, peak and duration of action can influence the ability of a particular insulin regimen to help control glucose levels. Patient factors, including individual variations in insulin absorption, levels of exercise and types of meals consumed, also influence the effectiveness of an insulin regimen. Rapid-acting insulin lispro is an ideal mealtime insulin. The premeal dose of insulin lispro can be adjusted based on the content of the meal and the patient's blood glucose level. Intermediate-acting and long-acting insulins should not be given to account for the content of a specific meal. Long-acting insulin can be administered once daily at bedtime or, ideally, twice daily in addition to another type of insulin. Patients with type 1 diabetes typically require an insulin dosage of 0.5 to 1.0 unit per kg per day. Newly diagnosed patients may have lower initial requirements because of continued endogenous insulin production. Flexible insulin regimens are based on predetermined actions in response to self-monitoring of blood glucose levels and carbohydrate intake.