It has long been established that achieving optimal glycemic control in T1DM prevents and reduces the risk of developing microvascular and cardiovascular complications [12, 13]. Consequently, the ADA generally recommends an HbA1c target of less than 7% in non-pregnant adults and less than 7.5% in children and adolescents with T1DM [8, 14].
The best-case scenario of T1DM management is to extend the time of glycemic control while avoiding hypoglycemia and ketosis; or as described by the ADA workgroup “a lifetime of euglycemia without hypoglycemia” [11, 15]. In our study, less than third of our population (27.4%) were adequately controlled, with a mean HbA1c of 8.11% at the study visit (higher than the targeted HbA1c by an absolute value of 1.11%). Two months prior to study entry, 42% of the patients experienced probable symptomatic hypoglycemia (defined by the ADA workgroup as an event with typical symptoms of hypoglycemia which is not accompanied by determination of plasma glucose concentration) [11]. These numbers hint that the glycemic control of T1DM in Kuwait, UAE, Bahrain and Oman is sub-optimal. One reason for this might be the lack of self-monitoring of plasma glucose levels. This problem of suboptimal glycemic control is not unique to our region. Despite the advancements in T1DM technology over the past decade, suboptimal glycemic control remains a worldwide problem [16, 17]. In a recent global cross-sectional study by Renard et al., 24.3% of T1DM patients achieved HbA1c < 7%, with mean HbA1c being 7.95%. The lowest rate of glycemic control was in the Middle East (18.9%); with mean HbA1c being 8.21% which is very similar to the mean HbA1c observed in our study (8.11%) [18]. However, the rate of documented symptomatic hypoglycemia 2 months preceding our study was less than that reported for the Middle-Eastern population 3 months preceding the study by Renard et al. (31.8% vs 37.2%, respectively). Similarly, the rate of severe hypoglycemia in the previous 2 months to our study was less than that reported in the 6 months preceding the study by Renard et al. (1.9% vs 14%) [18]. A main contributing factor to these differences is the time in months during which hypoglycemia was measured.
In a cross-sectional survey of 17,000 Japanese patients with diabetes that aimed to describe glycemic control in Japan from 2000 to 2002, baseline characteristics of 793 T1DM patients were recorded. The mean HbA1c of T1DM patients in the Japanese study was 7.8% which is lower than that found in our study. In addition, the Japanese study population was older [mean age of 47 (15.8) vs 31.6 (9.4) years in our study], had lower BMI [22.4 (3.1) vs 26.2 (5.0) Kg/m2], similar systolic [124.5 (17.3) vs 121.2 (14.4) mmHg] and diastolic blood pressure [73.3 (10.2) vs 73.8 (9.4) mmHg], higher total serum cholesterol [199.6 (36.5) vs 126.8 (34.8) mg/dL] and higher level of triglycerides [101.3 (100.6) vs 97.4 (36.3)] [16].
Surprisingly, some patients in our study received other diabetes drugs (namely metformin, DPP4 inhibitors, SGLT2 inhibitors, and GLP1 receptor analogs) besides their insulin regimen. Although none of these medications is approved for use in T1DM, these were all prescribed “off-label”. The notion of adjunctive therapy in T1DM has been circulating in clinical practice for quite some time. Adjunctive therapies are usually used to reduce insulin dose requirements, contribute to more HbA1c reduction, and cause weight loss [19]; we speculate that they were used in this study for the same reasons. When metformin was added to insulin therapy in T1DM patients, small reductions in body weight, BMI, and lipid levels, as well as reduced insulin requirements were observed without improvements in HbA1c [20]. Furthermore, a systematic review and meta-analysis conducted by Wang et al. in 2018 found that the additional use of DPP4 inhibitors resulted in a greater (although not significant) reduction in HbA1c levels and a small reduction in postprandial glucose or insulin dose compared to insulin monotherapy. Despte this, Wang et al. did not support the addition of DPP4 inhibitors in real-life clinical management of T1DM [17]. Further, SGLT2 inhibitors in combination with insulin led to HbA1c improvement and body weight loss (but was associated with increased DKA risk) compared with insulin alone in inadequately controlled T1DM patients [21, 22]. Moreover, the addition of a GLP1 receptor agonist to insulin caused small HbA1c improvements as well as weight loss compared to insulin alone in T1DM patients [23].
Given that about 2.2% of our patients were neither on prandial nor premix insulin, it is worth mentioning that a small percentage of patients enrolled in this study could have been affected by latent autoimmune diabetes in adults (LADA). It is possible that they may have been registered as T1DM because they were positive for glutamic acid decarboxylase antibodies (GADA), but – due to their preserved beta cell function – did not necessarily require treatment with multiple daily insulin injections [24]. According to the study conducted by Maddaloni et al. in the UAE, 2.6% of 18,101 subjects with adult-onset diabetes had LADA [24]; a percentage approaching the 2.2% not receiving prandial or premix insulin in our study. O’Neal et al. highlighted that correct diagnosis and early treatment are crucial to evade long-term complications of poor glycemic control [25]. Therapy should aim to achieve glycemic control and preserve the ability of beta cells to secrete insulin [26]. An international expert panel concluded that DPP4 inhibitors or GLP1 receptor agonists may improve glycemic control in LADA patients (unless c-peptide levels are very low in the latter). It also suggested that SGLT2 inhibitors may be particularly promising in overweight LADA patients [26]. Considering that metformin was the most commonly prescribed medication among non-insulin antihyperglycemic drugs in our study, we should highlight that the mentioned expert panel concluded that the efficacy of metformin in LADA was inconclusive [26].
According to the recent position statement by the ADA, nearly 30% of T1DM in children and adolescents presents as diabetic ketoacidosis (DKA). However, DKA was employed in the diagnosis of only 8.7% of our study population. In our study, the most commonly used method for confirming diagnosis of T1DM was the random blood sugar test. The position statement also pointed out that the female to male ratio in children and adolescents with T1DM is usually 1:1; much similar to ours (it should be noted that our study did not include children but included adolescents and adults) [14].
Although several studies found a higher prevalence of dyslipidemia in children and adolescents with T1DM compared to controls [18, 27], the lipid profile of our study population at diagnosis of T1DM was optimal according to the goal levels suggested by Orchard et al. in 2001 [low-density lipoprotein (LDL) cholesterol < 100 mg/dL (2.6 mmol/L), high-density lipoprotein (HDL) cholesterol > 45 mg/dL (1.1 mmol/L), triglycerides < 150 mg/dL (1.7 mmol/L)] [19]. However, it should be emphasized that guidelines set by the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS) for the management of dyslipidemias recommend reducing LDL cholesterol by at least 30% with statins in all T1DM patients with microalbuminuria and renal disease regardless the value of baseline LDL cholesterol [20]. In addition, most of our patients were normotensive.
Based on multivariate regression analysis, the main variables associated with adequate glycemic control in our study were low HbA1c at the time of diagnosis and absence of a family history of diabetes. A recent retrospective Jordanian study found that younger age, dietary compliance, receiving insulin at school, high grades in school, and the presence of direct mother care; were all associated with better metabolic control in T1DM Jordanian children [28].
Given that 96.2% of our study population resided in urban settings and 59.4% were employed, our results should not necessarily represent people with T1DM who are unemployed or those who live in rural areas. Given also that people who live in rural areas often face difficulties in accessing optimal healthcare and in adhering to the standard of diabetes care [21, 22], it should be expected that glycemic control in such population would be even less than that found in our study.
We believe that there are some obstacles opposing the uptake of educational programs (i.e. leading to poor attendance) in the region. Further studies are needed to determine whether these obstacles stem from clinicians not referring their patients to the programs or from patients not complying. Findings of such studies would be crucial to improve attendance in our hospitals.
The main strength of our study lies in the amount of data collected from T1DM patients in the participating centers. However, a few limitations exist. The exact names of insulin analogs and the duration and nature of diabetes educational programs were not recorded. In addition, the degree of adherence to insulin regimens and the QoL of patients were not assessed.
