The IDMPS Wave 7 sub-analysis showed that many people with T2D in LMIC are treated with OADs alone despite poor glycemic control. In addition, the GOAL study showed that insulin initiation or intensification significantly reduced HbA1c levels (−2%) in poorly controlled participants . The panel of experts compared these results with those obtained in high-income countries in order to define plausible preventive strategies.
Therapeutic Inertia in LMIC Compared to High-Income Countries
The results of the IDMPS Wave 7 sub-analysis were compared with those obtained in Western countries, where trends on glycemic control are well known [15, 16]. The rate of insufficient glycemic control in that sub-analysis, 63% in patients with diabetes duration between 5 and 12 years, was higher than that observed in the NHANES survey in the USA  and in the GUIDANCE study in European countries  (Fig. 2). These data, as well as the GOAL data, suggest significant opportunities for improving glycemic control in LMIC.
Barriers to Insulin Therapy
In the UK, a retrospective cohort study based on 81,573 people with T2D  showed that many of the patients experienced years of inadequate glycemic control due to delays in treatment intensification, especially when insulin treatment was needed. Moreover, once insulin therapy has been initiated, many patients fail to reach glycemic targets . Glycemic control is suboptimal across geographic regions and in both low- and higher-income countries, and delays of 3 years or more are frequent before an initiation or intensification of diabetes treatment [19, 20].
Multiple factors related to the patient and the physician contribute to the resistance to insulin initiation, titration and/or intensification stages . The reasons for this include poor access to medicines and medical care, fear of daily injections and hypoglycemia by the patient, poor communication, lack of experience in primary care by the physician and lack of time and/or resources .
In LMIC, Casciano et al.  showed that the possibility of oral administration instead of injectable therapies was a determining factor for not initiating insulin, while the risk of hypoglycemia symptoms had a much lower influence on treatment decision. Experience with insulin treatment and diabetes education significantly improved insulin use . Aschner et al.  showed that fear of hypoglycemia, lack of insulin titration and costs were the most common reasons for not intensifying insulin therapy. Finally, patients’ education modestly, but significantly improved the number of patients achieving HbA1c target values in LMIC (38.1 vs. 35.8% without diabetes education) and increased their insulin use .
Diabetic Complications and Mortality in LMIC Versus High Income Countries
Diabetes is a silent disease for many patients, which increases cardiovascular mortality in the long-term and/or generating serious microvascular complications, such as kidney failure, retinopathy and severe foot infections leading to amputation . Poor glycemic control is common in patients in developing countries as compared to those in developed ones. For example, the rate of insufficient glycemic control reported in this IDMPS Wave 7 sub-analysis, namely 63% in patients with diabetes duration between 5 and 12 years, was higher than that observed in the NHANES survey in the USA  and the GUIDANCE study in European countries  (Fig. 2). Similarly, in LMIC a relatively lower percentage of patients were screened for diabetes-related complications, such as retinopathy, as compared to evaluations made in the USA and Europe (Fig. 3). Additionally, the rate of microvascular diabetes complications in the Wave 7 population (50.7% for a diabetes duration between 5 and 12 years) was much higher than the rate observed for a similar diabetes duration in European countries (27.7%) .
The estimation of mortality due to diabetes in some LMIC has been problematic since no reliable data are available and also because people with diabetes are more frequently reported to die of “cardiovascular disease” or “kidney failure,” instead of “a diabetes complication” . Roglic and Unwin  used a computerized disease model and estimated that approximately four million deaths related to diabetes occur each year, with 80% of them in LMIC. Global comparisons have also shown that some countries experience high rates of hypoglycemia-related mortality . To our knowledge, the influence of glycemic control on diabetes mortality has not been investigated in LMIC.
With proper changes in lifestyle, as well as early diagnosis and intervention, many people with diabetes can delay the onset of complications and attenuate tissue damage [26, 27]. In particular, annual screening for chronic diabetes complications is recommended in treatment guidelines .
In LMIC, Gagliardino et al.  reported annual screening rates of 69.0% for retinopathy (retina examination), 62.5% for neuropathy (monofilament test), 83.9% for nephropathy (blood or urine test) and 73.4% for foot ulcer. It is of interest to note that while screening values for retinopathy in LMICs are lower than those reported for European countries (GUIDANCE study)  and for the USA (NHANES survey) , screening for foot ulcer compares well with those noted in the developed countries (Fig. 3). Moreover, Gagliardino et al.  also showed educated patients had significantly lower rates of both foot ulcer (− 31%) and peripheral vascular disease (− 26%), and higher insulin use.
Role of Patient and Healthcare Education for Better Glycemic Control in LMICs
Previous studies have indicated that lack of proper education related to diabetes is a predictive factor for poor glycemic control . For example, in the IDMPS Wave 5 survey, although 78.3% of the patient population has received diabetes education, very few patients received a structured educational course by certified diabetes instructors; rather, the majority received it from physicians . Moreover, only half of the population in these LMICs followed a healthy diet and had a regular physical exercise plan . This poor awareness of diabetes disease management is clearly reflected by finding that < 50% of the patients achieved the target HbA1c of < 7% . Similar observations have been reported from other studies, highlighting the importance of disease education as a management strategy for better glycemic outcomes. Thus, there is a need for a more structured and systematic education of patients with respect to how to manage their disease so as to avoid uncontrolled glycemic control over the long term, with the ultimate aim to prevent diabetes disease-related complications.
Strengths and Limitations
This expert opinion reflects the existing scenario of diabetes prevalence, incidence and diabetes care in LMICs, based on an analysis of the two recent and large registries performed in some of the developing countries from different regions of the world. The strength of this expert opinion is that it is based on the two studies with a large sample size and a global representation outside Europe and North America, and is instrumental in evaluating the prevailing diabetes conditions in developing countries as compared to the developed countries. However, the major limitation of this expert opinion is that it is representative in nature and allows only a summation of data rather than actual measurements.
In LMIC, many people with diabetes receive a late diagnosis, at the time when patients present with retinopathy, nephropathy, foot ulceration and other complications, with a consequent loss of treatment efficacy . Most of the direct costs of T2D treatment are due to diabetes complications [8, 31,32,33,34,35]. This is particularly true in the case of hospitalizations due to diabetes complications, which mobilize many human resources and require expensive medical procedures (i.e. leg amputations) [5, 36]. Therefore, the burden of diabetic complications in LMIC represents a dramatic challenge for healthcare providers and patients.
The costs of improving glycemic control and other preventive measures are less than the costs of inpatient hospital care and the treatment of diabetes complications (60% of the total medical costs) . Moreover, health expenditure attributable to diabetes is much lower in LMIC than in high-income countries . Improving both glycemic control and a patient’s education should be the short-term strategies of choice in LMICs.
Finally, specific clinical practice recommendations for LMIC are urgently needed. We suggest that healthcare providers focus on appropriate treatment guidelines (American Diabetes Association/European Association for the study of Diabetes and recommendations therein and on local country recommendations/consensus guidelines) which emphasize early diagnosis, systematic screening for complications and proper and timely treatment intensification.