Diabetes mellitus is a disease characterized by metabolic dysregulation, including abnormal glucose metabolism, with characteristic long-term complications. Complications specific to diabetes include retinopathy, nephropathy, and neuropathy. Patients with all forms of diabetes of sufficient duration, including type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM), are vulnerable to these complications, which result in serious morbidity. These are microvascular complications. High blood sugar is the driver of microvascular complications in diabetes. Say no to plagiarism. Get a tailor-made essay on “Why violent video games should not be banned”? Get an original essay To achieve glycemic goals in patients with type 2 diabetes, several pharmacological agents, including sulfonylureas, meglitinides, metformin, alpha-glucosidase inhibitors, thiazolidinediones, dipeptidyl peptidase IV (DPP-4) inhibitors, glucagon-like peptide 1 (GLP-1) receptor agonist, and insulin are available. These agents can be used alone or in combination to achieve target glycemic control. Unlike type 1 diabetic patients who do not have significant insulin secretion and therefore require insulin therapy from the onset of their disease, in type 2 diabetic patients insulin resistance with hyperinsulinemia is an important feature. in the early stages of the disease. People with type 2 diabetes mellitus thus benefit from measures to improve insulin sensitivity, such as dietary calorie restriction, exercise and weight management early in their disease, in combination with oral agents. such as insulin sensitizers and insulin secretagogues, to achieve the glycemic target. With the progression of type 2 diabetes, there is ultimately a progressive loss of pancreatic beta cell function and a reduction in endogenous insulin secretion. At this point, most patients will require exogenous insulin therapy to achieve optimal glycemic control. Landmark clinical trials have established that optimal glycemic control can prevent/delay the progression of complications in people with diabetes mellitus1. The findings of these trials strategically position insulin as a very important agent in reducing microvascular complications1,2. Data from the United Kingdom Prospective Diabetes Study (UKPDS) suggest that early insulin treatment reduces macrovascular risk in type 23 diabetes mellitus. These trials aim to achieve glycemic control below which no complications would occur. However, better glycemic control was associated with reduced risk of complications across the entire glycemic range (“the lower the better”) in the UKPDS4. In the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study, higher mortality was recorded in the intensive blood glucose treatment group while targeting HbA1C of <6.0% compared to the standard treatment group targeting HbA1C of 7.0 to 7.9%5. The intensive arm recorded more episodes of hypoglycemia, hence the increase in mortality recorded5. No additional benefit was recorded by lowering HbA1C <6.5% in the KUMAMOTO 2 study. Choosing among the wide variety of glucose-lowering interventions currently available could pose a challenge for the healthcare provider and patients in terms of effectiveness, tolerability and cost. the different treatments for diabetes. However,this should not be the case, as reductions in the risk of long-term complications were related to the levels of glycemic control achieved, rather than to a specific hypoglycemic agent 1. In the Steno-2 study, very few patients had reached the HbA1C level. target of 6.5% compared to the large number of patients who achieved the intensive blood pressure and serum lipid targets6. The challenges of initiating and intensifying insulin therapy are enormous and could be intimidating for caregivers. This review contains an overview of currently available insulin preparations and an overview of the advantages and disadvantages of different regimens commonly used for initiation and intensification of insulin therapy in patients with type 2 diabetes. Our aim is to to help clinicians design individualized management plans for insulin therapy in patients with type 2 diabetes. Why insulin therapy in type 2 diabetes Three major pathophysiological abnormalities contribute to hyperglycemia in type 2 diabetes : excessive hepatic glucose production, impaired pancreatic insulin secretion and peripheral resistance to insulin action occurring mainly in the liver and muscle tissues1. Among these, peripheral resistance to insulin action and impaired pancreatic beta cell secretion are early and primary abnormalities, while increased hepatic glucose production is a late and primary manifestation. secondary. Early in their disease, patients with type 2 diabetes compensate for increased insulin resistance at the tissue level by increasing insulin secretion from pancreatic beta cells. When this compensation is no longer sufficient to overcome insulin resistance, blood sugar begins to rise. However, over the course of the disease, insulin levels slowly begin to decline and, ultimately, most patients with type 2 diabetes mellitus fail to achieve optimal glycemic control with oral agents1. At this stage, the introduction of insulin is inevitable. Human insulin and its analogues Insulin therapy with conventional basal and mealtime insulin preparations has many disadvantages. First, the absorption of ordinary human insulin by the subcutaneous tissue is slow, and the metabolic action takes effect only 30-60 minutes after injection and reaches its maximum after 2-3 hours. Therefore, treatment with regular insulin is associated with postprandial hyperglycemia and an increased risk of late postprandial hypoglycemia. Second, conventional NPH basal insulin has a distinct maximal hypoglycemic effect, has a duration of action considerably less than 24 h, and is absorbed by the subcutaneous tissue at variable rates. These pharmacodynamic limitations predispose users to high pre-breakfast glucose levels and nocturnal hypoglycemia 7,8. To overcome these difficulties, insulin analogues with a modified amino acid sequence from the human insulin molecule have been developed. All three fast-acting analogs (except glulisine and lispro) are absorbed more quickly than regular insulin due to reduced self-association. Their onset of action occurs within 15 minutes after subcutaneous injection and their maximum action is faster and greater. Long-acting insulin analogues (detemir and glargine) have a limited maximum effect and a longer average duration of action than NPH insulin (with glargine having a slightly longer action than detemir)9-11. The pathophysiological process of diabetessweet type 2 leaves the patient with residual insulin production against a background of insulin resistance. It should be noted that long-acting insulin analogues have pharmacokinetics that closely mimic the physiological secretion of insulin in the body. When to start insulin therapy? This question will arise at some point in the management of patients with type 2 diabetes mellitus, a progressive and chronic disease. The answer is not simple. This leaves room for controversy. Oral medications are traditionally introduced in stages, with insulin reserved as the final step in the management of type 2 diabetes mellitus. It can take up to 10 to 15 years after diagnosis before insulin is finally introduced. Fears of painful injections, weight gain and hypoglycemia militate against early initiation of insulin by both doctors and patients13,14. Negative beliefs about insulin treatment and other sociocultural factors also affect patients' acceptance of insulin. 14, 15 This predisposes the patient to long-term complications due to exposure to many years of insulin treatment. uncontrolled hyperglycemia16. This therefore requires a proactive approach to therapeutic failure. Reducing blood glucose improves insulin resistance as well as insulin secretion17. Early initiation of insulin therapy in a newly diagnosed patient with type 2 diabetes mellitus restores and maintains β17 cell function. We recommend that insulin be initiated when a stepwise approach has not achieved the goal of HbA1C <7%18. This initiation must be rapid when the HbA1C level < 7% is not reached after 2 to 3 months of dual oral therapy at maximum dose. For patients who are intolerant to one or more oral hypoglycemic agents and who are unable to control their blood glucose with oral monotherapy, as well as for those with a personal preference, earlier initiation of insulin is indicated. It should be noted that the rapid addition of insulin therapy is supported by numerous studies showing improved treatment satisfaction and quality of life in type 2 diabetic patients who have started using insulin19,20. How to initiate insulin therapy? Good glycemic control was achieved in the majority of patients with type 2 diabetes mellitus in “treat to target” clinical trials when basal insulin was added to their oral antidiabetic agents21-23. It should be noted, however, that the benefit of long-acting insulin analogues lies in the reduction of nocturnal hypoglycemia24. According to the ADA/EASD algorithm for the management of type 2 diabetes, insulin could be initiated either with NPH insulin once daily or with a long-acting insulin analogue18. A meta-analysis including six randomized comparisons of NPH and glargine revealed event rates for self-monitoring blood glucose (SMBG) that confirmed symptomatic hypoglycemia <65 mg/dL of only 138 and 91 events per 100 patient-years for these insulins, respectively, in insulin-naïve type 2 diabetic patients who achieved an HbA1c level of 7.0%25. NPH, insulin glargine, and insulin have been used as basal insulin to achieve glycemic control in patients with type 2 diabetes. As desirable as it may be, the financial consequences of the new insulins for the patient should not be ignored by doctors. In Africa (and Nigeria), the cost of insulin constitutes an obstacle to the acceptance of insulin therapy, beyond sociocultural problems15. NPH is cost-effective and insulin therapy inType 2 diabetes can be initiated with NPH. The other issue to consider is the frequency of basal insulin administration. In a “treat to target” trial with twice-daily administration of detemir, an HbA1c level of 6.8% was achieved.22 In other studies, a second daily injection of detemir was required in 34 to 55% of study subjects due to pre-injection. -dinner hyperglycemia or nocturnal hypoglycemia. 23,26 In the only reported trial that studied the effectiveness of once-daily insulin detemir, HbA1c remained above the currently recommended glycemic target with a final level of 7.4%, both for NPH insulin than for insulin detemir, 27 compared to end-of-study A1C. <7.0% with glargine and NPH once daily in the original Treat-to-Target trial.21 In the ACCORD5 study, the finding of increased mortality in the intensive treatment group to lower blood glucose will likely deter some practitioners reduce blood sugar levels quickly. The ACCORD study included only patients at high risk of cardiovascular disease, in whom low HbA1c levels were achieved using up to four or five different classes of glucose-lowering medications. In contrast, in less selected patients treated with stable doses of one or two oral agents, simple titration algorithms targeting a fasting blood glucose = 100 mg/dl (= 5.6 mmol/l) can safely achieve an HbA1C level of 7.0%. 21 A patient-driven algorithm, in which patients increase their insulin dose by 2 or 3 units every 3 days, as long as their fasting blood glucose remains above target, is a practical approach that has been shown to just as effective, if not more so. than physician-directed titration. 28,29 In once-daily basal insulin regimens, evening administration of NPH appears to be superior to morning injection7,19. The results of studies investigating the injection time of long-acting insulin analogues are conflicting. When insulin glargine injection in the morning and evening was compared in one study, there was a greater reduction in HbA1c and nocturnal hypoglycemia when insulin glargine was administered in the morning30, whereas in another larger study with an identical design, no significant differences were found in timing31. Morning administration of insulin detemir was associated with lower daytime glucose levels and a trend toward a reduced risk of nocturnal hypoglycemia compared to evening injection27. What does all this mean? We can confidently conclude from these conflicting data that when nocturnal hypoglycemia limits dose titration of detemir or glargine in the evening, morning administration could be attempted. Other options exist for initiating insulin therapy. The Targeted Therapy in Type 2 Diabetes (4-T) Study compared various insulin initiation options. Basal insulin introduced at bedtime has been compared to either biphasic insulin twice daily or prandial insulin before meals26. Regimens using biphasic or prandial insulin were found to reduce HbA1c to a greater extent than basal insulin, but were associated with higher risks of hypoglycemia and greater weight gain26. The reduction in HbA1c with biphasic insulin is equivalent to prandial insulin. However, there is greater weight gain and more hypoglycemia than with basal insulin but less for both than with prandial insulin26. Prandial insulin initiation is not a first choice approach when initiating insulin in diabetes..