1.1 Introduction
Diabetes mellitus is a group of metabolic disorders characterized by abnormal glucose, fat, and protein metabolism. The defining feature of diabetes is hyperglycemia which leads to acute complications like DKA, HHS, or chronic micro-and macrovascular complications like nephropathy, neuropathy, retinopathy, cardiovascular diseases. Diabetes occurs due to an absolute or relative deficiency of insulin secretion along with a varying degree of peripheral resistance to insulin action.[1–4]
Globally the prevalence of diabetes reached 463 million in 2019 and this is estimated to reach 578 million by the year 2030 and 700 million in 2045.[5] Around 4 million deaths were caused by diabetes in the year 2012 and this includes 1.5 Million deaths related directly to diabetes and additional 2.2 million deaths due to complications related to diabetes (cardiovascular disease, chronic kidney disease, and tuberculosis) in 2012. In Africa, the total number of adults with diabetes is 19.4 million from those 1.7 million are Ethiopians.[6, 7] Previous studies have shown that the prevalence of diabetes in Ethiopia is around 6.5%in urban areas and 1.9% in a rural setting.[8, 9] A recent STEPS survey done by the Ministry of Health has found a prevalence of 3.2%.[10]
According to the WHO 2019 classification of diabetes, it is classified as Type 1 which is mainly immune-mediated β-cell destruction, Type 2 which is characterized by impaired insulin secretion with peripheral insulin resistance, Hybrid type which has both features of type 1 and types 2, Other Specific types, Unclassified which is a temporary classification until we do the investigations and observe the clinical course and hyperglycemia first detected during pregnancy.[1]
Type 2 Diabetes is the most common type accounting for around 90% of the cases.[11, 12] The proportion of patients with Type 2 DM which is undiagnosed varies from 24-62% across regions in the world.[7] Of all patients with Type 2 DM, 40% of the patients are asymptomatic during diagnosis and from those asymptomatic patients, 32% of them will have a microvascular complication at the time of diagnosis.[8]
As patients with type 2 diabetes are mostly asymptomatic during diagnosis and around 32% of them already have a microvascular complication during diagnosis achieving good glycemic control has shown significant benefit in different large clinical trials. The UKPDS trial showed significant benefit (12% reduction) in terms of diabetes-related endpoints (sudden death, death from hyperglycemia or hypoglycemia, fatal or non-fatal myocardial infarction, angina, heart failure, stroke, renal failure, amputation [of at least one digit], vitreous hemorrhage, retinopathy requiring photocoagulation, blindness in one eye, or cataract extraction); diabetes-related death (death from myocardial infarction, stroke, peripheral vascular disease, renal disease, hyperglycemia or hypoglycemia, and sudden death); all-cause mortality from an intensive glycemic control group and most of this benefit come from a reduction of microvascular complication by 25% and there was a borderline statically significant benefit in reducing Macrovascular complications. This was also proven in the long-term follow-up of these patients.[13, 14] In the Kumamoto study type 2 diabetic patients assigned to the intensive glycemic control group were shown to benefit from the treatment and lower incidence and progression of retinopathy and nephropathy were documented after 6 years of treatment.[15]
The ADVANCE trial in patients with intensive glycemic control (HgA1C -6.5%) has shown a 10% reduction in the combined outcome of macrovascular as well as microvascular events mainly due to a 21% relative reduction in nephropathy. In the ACCORD trial which relatively involved patients with long-standing Type 2 DM, there was a reduction of microvascular complications like retinopathy, nephropathy. But there was increased cardiovascular mortality in the intensive arm and the study was discontinued early.[16–18]
The VADT trial was performed to define the benefit of intensive glycemic control in patients with poorly controlled long-standing Type 2 DM with a mean duration of 11.5 years after diagnosis with 40% of the patients already with cardiovascular events. There was no difference in the occurrence of cardiovascular events between the intensive and conventional treatment groups.[19]
Target HgA1C levels in Type 2DM patients should be individualized according to the patient life expectancy, the already developed micro and macrovascular complications. Generally, the target HgA1C level is <7%. However, in those patients with long-standing diabetes with complications, elderly, children, comorbidity, and those with recurrent hypoglycemia and difficult to control diabetes despite appropriate therapy including insulin the less stringent target (<8%) is appropriate.[20]
The treatment of Type 2 DM starts with diabetes education, lifestyle measure, and prevention of microvascular and cardiovascular complications, and avoidance of drugs that exacerbate micro and macrovascular complications. The first-line pharmacologic treatment is Metformin unless contraindicated. The other treatments depend on whether there are established cardiovascular diseases or not, HF or CKD. If ASCVD or CKD predominates the preferred management will be GLP-1 RA or SGLT2i with proven CV benefit and should be started if the eGFR allows. If the priority is weight loss and Metformin is the first-line therapy and if still, the HgA1C is high, the addition of SGLT2i or GLP-1 RA or Addition of DPP-4 is possible. If cost is the major issue after we start the patient on metformin, we can add SU or TZD, and if still there is high HgA1C we can add basal insulin. For patients with HgA1C >10% or 2% above target HgA1C despite triple or dual therapy we have to consider to start the patients on injectable GLP-1 RA initially and if the HgA1C is still above the target we have to start the patients on basal insulin but if the patient has HgA1C >11% and has symptoms and evidence of catabolism like weight loss, polydipsia or polyuria we have to consider insulin as a first-line injectable. To avoid inertia we have to assess each patient every 03-06 months.[21–23]
Eventually, many patients with Type 2 DM will require insulin therapy; so, we have to educate all patients about the possibility of the need for insulin therapy and we have to counsel them not to consider it as a personal failure.
1.2 Literature review
Type 2 Diabetes is a group of metabolic disorders characterized by insulin resistance and progressive absolute insulin deficiency due to β-cell depletion over the years. Insulin could be used as initial therapy in patients with severe hyperglycemia at presentation and with catabolic features, patients with difficulty to differentiate the type of diabetes, or after oral hypoglycemic therapy failed to control hyperglycemia. [21][24]
Achieving tight glycemic control as early as possible after the diagnosis of type 2 DM has shown to be beneficial in preventing microvascular as well as macrovascular complications as shown in the UKPDS study.[13] Despite this evidences, there is significant clinical inertia on initiating and intensifying oral medication as well as initiating insulin therapy when indicated.[25]
As we go through works of literature there are multiple reasons quoted by the physicians as well as by patients for not initiating or accepting insulin therapy.[26] GAAP study is a multi-centered survey conducted in 8 countries. Most physicians on this survey report that many insulin-treated patients do not have adequate glucose control (87.6%) and they would have treated aggressively if not for the fear of hypoglycemia. The majority of patients and /or physicians regard insulin treatment as restrictive, more patients see insulin treatment as positive than negative impact on their lives. [27] Another international survey DAWN study involving 13 countries showed patients and provider attitudes about insulin therapy differ significantly. Patients rate the clinical efficacy of insulin as low and blame themselves if they had to start insulin. Patients who are not managing their diabetes well consider insulin therapy as beneficial. Most nurses and general practitioners (50–55%) delay insulin therapy until necessary, but specialists and opinion leaders are less likely to do so.[28]
The DIPP FACTOR, a prospective observational study done in Korea shows patients' related factors for delay in insulin initiation included older age, shorter duration of diabetes, and lower HgA1C. Physicians related factors included age between 50-60, women sex, and the number of patients consulted per month <1000 especially patient's refusal (33.6%) and physician's concern of patient's noncompliance (26.5%) were the major physician reported reason for delaying insulin therapy. The inconvenience of insulin therapy (51.6%) and fear of injection (48.2%) were the major reason for the patient’s refusal.[29]
Patients from China gave the following reason for resisting insulin therapy: inconvenience (64.3%); concerns over addiction (24.6%); pain (14.3%); side effects (14.1%); and high cost (13.6%).[30] In a study done at Turkish primary care, most patients (57.4%) considered that insulin was a drug of last resort; 34% thought that insulin lowered blood glucose level to an extreme degree and 14.9% disagreed. 27.6% of them thought self-injection was hard, another 27.6% required someone else to administer the injection, 33% say insulin injection was painful.[31]
According to a Caribbean study done in Trinidad, factors that delay insulin therapy included limited knowledge concerning insulin therapy, failure to conduct a regular and routine assessment of HgA1C values, perception of insulin being painful, fear of needle, hypoglycemia, weight gain, scaring at the injection site and embarrassment were specific barriers.[32]
A study from Kenya on psychological resistance to insulin in type 2 DM patients showed a prevalence of 82.6% and those who were already on insulin therapy have lesser psychological resistance compared to the non-insulin users.[33]
In Ethiopia in a study done at TASH majority of patients with type 2 DM have uncontrolled fasting glucose level and the factors which are significantly associated with poor glycemic control were longer duration of diabetes (AOR = 2.72 95%CI:1.16–6.32), and being on insulin therapy (AOR = 3.01 95% CI: 1.5–5.9).[34] There is no data for Ethiopia regarding patient's and physician's attitudes and knowledge in starting insulin in Type 2 diabetes.