Is insulin pump therapy effective in Type 1 diabetes?

There continues to be uncertainty about the effectiveness in Type 1 diabetes of insulin pump therapy (continuous subcutaneous insulin infusion, CSII) vs. multiple daily insulin injections (MDI). This narrative review discusses the reasons for this uncertainty, summarizes the current evidence base for CSII and suggests some future research needs. There are difficulties in interpreting trials of CSII because effectiveness varies widely due to factors such as differing baseline control, suboptimal use of best CSII practices, and psychological factors, for example, high external locus of control, non‐adherence and lack of motivation. Many summary meta‐analyses are also misleading because of poor trial selection (e.g. short duration, obsolete pumps, low baseline rate of hypoglycaemia) and reliance on mean effect size for decision‐making. Both MDI and CSII can achieve strict glycaemic control without hypoglycaemia in some people with Type 1 diabetes, especially those who are motivated and have undergone structured diabetes education, and with high levels of ongoing input from healthcare professionals. CSII is particularly effective in those people with Type 1 diabetes who have not achieved target HbA_1c levels without disabling hypoglycaemia using best attempts with MDI, and here there can be valuable and substantial improvement. Insulin pumps are safe, effective and accepted when used in newly diagnosed diabetes, particularly in children, where MDI may not be practicable. Future research needs include more studies on mortality associated with insulin pumps where registry data have suggested lower rates vs. MDI; and psychological strategies to improve non‐adherence and suboptimal glycaemic outcomes on CSII.     

Long-term outcome of insulin pump therapy in children with type 1 diabetes assessed in a large population-based case–control study

Aims/hypothesis

We determined the impact of insulin pump therapy on long-term glycaemic control, BMI, rate of severe hypoglycaemia and diabetic ketoacidosis (DKA) in children.

Methods

Patients on pump therapy at a single paediatric tertiary hospital were matched to patients treated by injections on the basis of age, duration of diabetes and HbA_1c at the time of pump start. HbA_1c, anthropometric data, episodes of severe hypoglycaemia and rates of hospitalisation for DKA were collected prospectively.

Results

A total of 345 patients on pump therapy were matched to controls on injections. The mean age, duration of diabetes at pump start and length of follow-up were 11.4 (±?3.5), 4.1 (±?3.0) and 3.5 (±?2.5) years, respectively. The mean HbA_1c reduction in the pump cohort was 0.6% (6.6 mmol/mol). This improved HbA_1c remained significant throughout the 7 years of follow-up. Pump therapy reduced severe hypoglycaemia from 14.7 to 7.2 events per 100 patient-years (p?<?0.001). In contrast, severe hypoglycaemia increased in the non-pump cohort over the same period from 6.8 to 10.2 events per 100 patient-years. The rate of hospitalisation for DKA was lower in the pump cohort (2.3 vs 4.7 per 100 patient-years, p?=?0.003) over the 1,160 patient-years of follow-up.

Conclusions/interpretation

This is the longest and largest study of insulin pump use in children and demonstrates that pump therapy provides a sustained improvement in glycaemic control, and reductions of severe hypoglycaemia and hospitalisation for DKA compared with a matched cohort using injections.     

Insulin therapy in pregnancy complicated by diabetes: are insulin analogs a new tool?

It has been demonstrated that good metabolic control maintained throughout pregnancy can reduce maternal and fetal complications in diabetes. To achieve good metabolic control, before conception and throughout pregnancy, insulin therapy needs to be optimized, and, in this context, the new insulins currently on the market may help. We therefore review here what is known about the potential benefits and risks related to the use of these new insulins in pregnancy. Clinical and experimental data on insulin lispro strongly suggest that lispro does not have adverse maternal or fetal effects during pregnancy in women with preexisting diabetes, and also that its use in these women results in improved glycemic control, fewer hypoglycemic episodes, and improved patient satisfaction. In women with gestational diabetes mellitus (GDM), the use of insulin lispro is efficient in reducing postprandial hyperglycemia and some neonatal features related to hyperglycemia, thus stressing its usefulness in this condition. As for insulin aspart, clinical data on GDM patients shows the same efficacy as insulin lispro in lowering postprandial hyperglycemia, indicating that insulin aspart may be used in GDM when this condition is characterized by postprandial hyperglycemia. The results of a multicentric study now in progress on the efficacy and safety of insulin aspart in type 1 pregnant diabetic patients will definitely be useful in establishing whether this insulin is safe in pregnancy. For the moment, the use of insulin glargine during pregnancy is not recommended owing to the lack of data on maternal and fetal effects.     

Is insulin resistance the principal cause of type 2 diabetes?

The data presented from these recent studies raise serious doubt concerning the commonly held view that insulin resistance is the principal cause of type 2 diabetes: first of all they provide evidence that insulin resistance may not be the primary genetic factor for type 2 diabetes; secondly, they demonstrate that at least under certain circumstances insulin resistance is not essential for diabetes to occur, and then finally, they indicate that insulin resistance may not be the predominant factor determining the degree of hyperglycaemia. Although these studies suggest that the role of insulin resistance relative to that of beta-cell dysfunction in the pathogenesis of type 2 diabetes has been generally overestimated, one should not be left with the impression that insulin resistance is not important. It is certainly an important factor in determining the degree of hyperglycaemia or glucose intolerance present at a given level of beta-cell function. The improvement in glycaemic control after weight loss which lessens insulin resistance or after the administration of pharmacologic agents that improve insulin sensitivity clearly argue that insulin resistance is important in this regard. In addition to influencing the severity of glucose intolerance, insulin resistance is probably also important in determining the time of onset of diabetes. It may do this simply by altering the balance between the body's demand for insulin and the ability of the pancreas to provide insulin. It might adversely affect beta-cell function in addition to increasing the demand for insulin. This concept is schematically represented in figure 3. It is well established that beta-cell function normally deteriorates as a function of age [41]. Although the prevalence of type 2 diabetes increases as a function of age, this by itself obviously does not result in diabetes in the great majority of people. In such individuals their insulin sensitivity is sufficient to maintain the balance between the supply and demand for insulin above the threshold for developing diabetes. Theoretically one may postulate three other situations originating with a genetic beta-cell defect: some people may start off life with normal beta-cell function but experience a genetically determined accelerated deterioration; some people may start off life with reduced beta-cell function (e.g. less beta-cell s); still others may start off with reduced beta-cell function and have an accelerated rate of deterioration. In each of the above situations, at any given level of beta-cell function, the degree of insulin resistance present would alter the threshold for developing impaired glucose tolerance and ultimately type 2 diabetes; in other words, the greater the insulin resistance, the lower the threshold, the earlier the onset and the more severe the diabetes will be. It follows therefore that efforts to diminish insulin resistance and to preserve beta-cell function should both be beneficial. Weight loss and increased physical activity, both of which reduceinsulin resistance, have been shown to prevent progression of people with impaired glucose tolerance to diabetes. Whether this is simply due to shifting the balance between insulin requirements and insulin availability or whether it also involves an improvement in beta-cell function and/or prevention of its deterioration remains to be clarified. Furthermore, it is not known whether pharmacologic agents which improve insulin sensitivity have similar effects.     

Does insulin therapy matter? Determinants of diabetes care outcomes

Objective

To evaluate adherence to care standards for people with diabetes (PWDs) on insulin therapy versus PWDs who are not on insulin therapy, controlling for social determinants.

High cumulative insulin exposure: a risk factor of atherosclerosis in type 1 diabetes?

BACKGROUND: Since insulin therapy might have an atherogenic effect, we studied the relationship between cumulative insulin dose and atherosclerosis in type 1 diabetes. We have focused on patients with type 1 diabetes instead of type 2 diabetes to minimise the effect of insulin resistance as a potential confounder. METHODS: An observational study was performed in 215 subjects with type 1 diabetes treated with multiple insulin injection therapy. Atherosclerosis was assessed by measurement of carotid intima-media thickness (CIMT). RESULTS: The cumulative dose of regular insulin showed a positive and significant relation with CIMT: increase of 21 microm in CIMT per S.D. of insulin use (95% CI: 8-35 adjusted for gender and age), which remained unchanged after adjustment for duration of diabetes, HbA1c, BMI, pulse pressure, physical activity and carotid lumen diameter. A similar relation was found for intermediate-acting insulin: 15.5 microm per S.D. (2-29), which was no longer present after further adjustment. CONCLUSIONS: These findings provide evidence that a high cumulative dose of regular insulin is a risk factor for atherosclerosis.     

Will oral semaglutide be a game-changer in the management of type 2 diabetes in primary care?

GLP-1 receptor agonists (GLP-1RAs) are recommended for patients with type 2 diabetes (T2D), particularly those at high cardiovascular risk. Oral semaglutide is the first oral GLP-1RA. In clinical trials, oral semaglutide 14 mg reduced mean HbA_1c by approximately 1.1–1.5% and reduced body weight by up to 5 kg. These changes were significantly greater compared with empagliflozin, sitagliptin and liraglutide (p < 0.05 for estimated treatment differences at 52 weeks in patients on treatment without rescue medication use). The most common side effects were gastrointestinal, mainly mild-to-moderate and transient nausea. Oral semaglutide may change the paradigm of T2D treatment in primary care.     

The benefit of aspirin therapy in type 2 diabetes: what is the evidence?

Many clinical guidelines recommend aspirin therapy for the prevention of cardiovascular events in individuals with type 2 diabetes. However it is unclear whether the level of evidence in guidelines is derived from studies carried out among individuals with diabetes. Medline and Embase databases were searched to retrieve studies published since 1990, evaluating the effect of aspirin on cardiovascular outcomes in subjects with type 2 diabetes. Four studies corresponded to the inclusion criteria. The three clinical trials retrieved could not prove from a statistical point of view, the benefits of aspirin therapy for subjects with type 2 diabetes. Reduction in cardiac mortality was found only in one observational study. Consequently, these findings suggest that the clinical guidelines have based their recommendations upon the expected benefit previously observed in other high-risk populations. Given the lack of hard evidence and the different well-known platelet physiology encountered in patients with diabetes, use of aspirin as a standard treatment at the highest level of evidence in guidelines for subjects with type 2 diabetes should be revisited.     

Will acarbose improve the metabolic abnormalities of insulin-resistant type 2 diabetes mellitus?

Individuals with type 2 diabetes mellitus (n = 105; age 36-71 years) on diet therapy alone, and with quite good glycaemic control (mean HbA1c approximately 7.0%) were randomized to receive acarbose (100 mg three times daily) or placebo for 16 weeks, and changes in clinical and metabolic parameters indicative of Syndrome X were monitored. Fasting levels of glucose, glycosylated haemoglobin (HbA1c), true insulin, proinsulin, fibrinogen and lipids were measured four times weekly, and glucose, insulin, proinsulin and triglyceride responses to a standardized 1.6 MJ breakfast were determined at 0, 1 and 2 h post meal. Analysis was on an intention-to-treat basis. Fasting levels of glucose (P < 0.0001), triglycerides (P = 0.03) and HbA1c (P = 0.003) were reduced by acarbose over the 16 weeks of treatment. The mean change in HbA1c from week 0 to 16 differed by 0.4% (P = 0.003) between the two groups. Insulin (P = 0.06), proinsulin (P = 0.07) and glucose (P < 0.0001) responses to the standard meal were reduced. These data show that acarbose reduces fasting glucose and triglyceride levels, lowers HbA1c and limits the glycaemic and insulin response to food in individuals with type 2 diabetes mellitus with Syndrome X. Pharmacological agents that improve the metabolic environment and reduce insulin resistance have the potential to limit the progression of atherogenesis associated with type 2 diabetes mellitus.