Critical Review
Type-2 Diabetes: Current Understanding
and Future Perspectives
Disease Biology Laboratory, Regional Centre for Biotechnology, National
Capital Region Biotech Science Cluster, Faridabad, Haryana, India
Abstract
The rapid outbreak of type-2 diabetes is one of the largest
public health problems around the globe. Particularly, the
developing nations are becoming the epicenters of cardiome-
tabolic disorders owing to the change in lifestyle and diet pref-
erence besides genetic predisposition. Diabetes has become a
major independent risk factor for cardiovascular diseases in
South Asian countries including India. The pathogenesis of
type-2 diabetes primarily initiates with inadequacy of pancre-
atic islet b-cells to respond to chronic fuel surfeit and hence
causing glycemic load, insulin resistance, and obesity. Urban
Indian life is threatened with unhealthy high calorie diet and
sedentary habits, and thus impairing the metabolic status of
thin-fat Indians and rendering them more vulnerable to met-
abolic disorders. Furthermore, the metabolic dysfunction may
Keywords: type-2 diabetes; insulin resistance; obesity; dyslipidemia;
intrauterine programming; thrifty phenotype and inflammation
Introduction
Cardiovascular diseases (CVDs) are the leading cause of mor-
bidity and mortality worldwide, accounting for approximately
17.3 million deaths per year, which is further estimated to rise
>23.6 million by 2030 (1). The high prevalence of obesity,
hypertension, diabetes, and dyslipidemia is closely associated
with the cardiovascular epidemic worldwide (2). Diabetes is
designated to be a major and independent risk factor for CVD
C 2015 International Union of Biochemistry and Molecular Biology
V
Volume 67, Number 7, July 2015, Pages 506513
*Address correspondence to: Prasenjit Guchhait, Disease Biology Labora-
tory, Regional Centre for Biotechnology, National Capital Region Biotech
Science Cluster, Faridabad-Gurgaon Expressway, 3rd Milestone, Faridabad,
Haryana 121001, India. Tel.: 191-1292848821.
E-mail: Prasenjit@rcb.res.in
Received 16 June 2015; Accepted 16 June 2015
DOI 10.1002/iub.1396
Published online 15 July 2015 in Wiley Online Library
(wileyonlinelibrary.com)
506
Ankita Pandey
Sheetal Chawla
Prasenjit Guchhait*
be triggered off quite early in life due to poor maternal health
and impairment in intrauterine programming and, particularly
in rural India. The impaired fetal development affects the
health status in later stage of life by promoting obesity, insulin
resistance, type-2 diabetes, and cardiovascular complications.
Therefore, the preventive and therapeutic approaches focus
on a holistic strategy to improve maternal and child health,
promote balanced diet and physical exercise in combination
with pharmacological intervention of reducing/checking hyper-
glycemia, obesity, and cardiovascular complications. This
review summarizes the epidemiology, mechanisms, and risk
factors for diabetes and cardiovascular disorders with a focus
on the Indian subcontinent. V C 2015 IUBMB Life, 67(7):
506513, 2015
in both men and women. About 65% diabetic patients die of
some form of heart disease or stroke (3). In addition, diabetic
patients with CVD sustain a worse prognosis for survival than
nondiabetic CVD patients and their quality of life is also com-
promised. WHO estimates that between 2000 and 2030, the
world population will increase by 37% and the number of peo-
ple with diabetes will increase by 114% (4). Conventional sta-
tistics based on population growth, ageing, and rate of urban-
ization in Asia show that India and China will be the two
countries with highest number of people with diabetes (79
4
and 42
3 million, respectively) by 2030 (5).
India is projected to have the largest CVD burden in the
world (6). The astounding upsurge in diabetes and CVD in Asia
particularly in India has been attributed to a paradigm shift in
the socioeconomic and demographic status, leading to rapid
urbanization as well as diet and lifestyle transition (7,8).
Besides being genetically susceptible, the Asian-Indian pheno-
type is also exposed to diverse environmental cues such as
unhealthy diet or sedentary lifestyle (9). Also, the intrauterine
programming including low birth weight, preterm birth, gesta-
tional diabetes, malnutrition, and maternal obesity results in
IUBMB Life
endocrine and metabolic dysfunctions, which cumulatively pre-
disposes them to acute obesity, insulin resistance, diabetes, or
CVD in later life (7,8). The pathomechanism of CVD in diabetic
patients is very complex being associated with clinical symp-
toms such as hyperglycemia, dyslipidemia, oxidative stress,
endothelial and hemostatic impairment, inflammatory load,
and renal dysfunction (10). Diabetes is associated with chronic
inflammation, characterized by the release of excess proin-
flammatory cytokines, abrupt levels of acute-phase proteins,
and other mediators, which are integral to the severity of car-
diovascular disorder (10).
This review, therefore, aims to provide an overview of the
current status of knowledge on diabetes and CVDs with a focus
on pathogenesis and risk factors involved in the disease pro-
gression and epidemiology, especially in Asian-Indian popula-
tion. In addition, we have also outlined the current advances
in the pathophysiology of CVD and have briefly addressed the
clinical manifestations and management strategies of patients
with diabetes.
Epidemiology and Prevalence of
Diabetes and Cardiovascular Risk
According to the reports by International Diabetes Federation
(IDF), 387 million people have diabetes, which is expected to
rise to 592 million by 2035 (11). Statistical data suggest that
the number of people with type-2 diabetes is increasing in
every country, but the low and middle income countries are
the most affected as they inhabit 77% of the total diabetic pop-
ulation (11). The situation is further worsened by the undiag-
nosed diabetes (fasting plasma glucose, >126 mg/dL) which
affects approximately 179 million people worldwide (11). How-
ever, there lies a significant gap in the knowledge of diabetes
and CVD epidemiology and associated risk factors among
Indian population.
Many developing nations such as India and China are
presently experiencing rapid urbanization and economic devel-
opment which has led to transition in nutrition patterns and
sedentary lifestyle, and thus giving rise to cardiometabolic dis-
orders. The Indian Diabetes Prevention Program (IDPP) (12)
suggests that after 3 years of follow-up, the relative risk reduc-
tion was reduced to 28.5% with life-style management, 26.4%
with metformin, and 28.2% with the combined interventions
compared with the control group. Urbanization reportedly
causes significant reduction in physical activity with increase
in body mass index (BMI) and upper body adiposity (13).
Urban populations can access more diverse diets and animal
food compared to rural residents, but it comprises of higher
intake of refined carbohydrates and processed foods, saturated
and total fat, and lower intake of fiber. The effect of such diet
pattern is significant as most of the emerging epidemic of
chronic disorders, such as diabetes, CVDs, stroke, and hyper-
tension, are diet related. Socioeconomic progression in a coun-
try transforms the living environments to be increasingly sed-
Pandey et al.
entary. The energy expenditure of Asian population has also
dramatically reduced owing to the occupational shift from
agricultural labor to that of employment in manufacturing
services (14), TV watching (15), sitting at work, and increased
mechanization and driving practices (16). The combination of
excessive energy intake and reduced energy output may ulti-
mately lead to obesity and insulin resistance.
The type-2 diabetes disease strikes the high prevalence
groups such as Pacific Islanders and southern Asians much
younger, among whom the onset of disease is very common in
the age group between 20 and 30 years (17). This trend is not
only alarming for the clinicians and medical community, but
also threatens to seriously hamper the countrys socioeco-
nomic development. For instance, in South India, there has
been a consistent escalation in the prevalence of diabetes in
younger population25.035.7% from year 2000 to 2006 (8).
The onset of glucose intolerance in women during preg-
nancy constitutes gestational diabetes, which usually reverts
after delivery. Few long-term studies in women with gesta-
tional diabetes for more than 10 years have shown a stable
long-term risk of type-2 diabetes of 70% (18). The concept of
gestational programming implies that during critical and sen-
sitive periods of fetal development, the nutritional and hormo-
nal imbalance in mother may permanently change structure,
physiology, and metabolism of fetus, consequently predispos-
ing individuals to specific disorders in their adult life (19). The
diagnosis of gestational diabetes mellitus (GDM) in a woman
predisposes her and her offspring towards increased risk of
developing glucose intolerance and obesity in future (20).
Approximately, four million women are diagnosed with GDM
annually in India and 50% develop type-2 diabetes within 5
years of pregnancy (21). This adds to the already existing huge
burden of diabetes patients (61.3 million in 2011), and also
contributes to the population at risk for diabetes and CVD, and
hence pressurizing the healthcare system in terms of both
direct and indirect costs (21).
In malnourished women, suboptimal fetal nutrition at criti-
cal points of time during intrauterine development may cause
permanent alterations in fetal structure, function, and metabo-
lism (thrifty phenotype/fetal origins) (22). Fetal under-
nutrition as a consequence of poor maternal nutrition results
in permanent endocrine and metabolic adaptations that
increase cardiometabolic disease risk in adulthood. The stud-
ies in animal models have shown that the offspring are born
with b-cell dysfunction and insulin resistance when their moth-
ers were subjected to insufficient calorie intake (23). Among
Indians, birth weight is shown to be associated with adult
type-2 diabetes phenotype (characterized by abnormal fat dis-
tribution, hyperinsulinemia, and insulin resistance) (2426). It
is interesting to explore the possibility as to whether this could
provide sufficient explanation for the increasing prevalence of
chronic noncommunicable diseases in India. The Pune Mater-
nal Nutrition Study, the Mysore Study, and the results from the
Vellore Birth Cohort have provided a wealth of information
favoring this association (2426). Despite several efforts to
507

improve maternal health, maternal malnutrition is a perennial
problem particularly in rural India.
In addition to malnourished mothers, Indian babies also
weigh the least in the world. An average Indian baby weighs
about 800 g less, and is leaner, compared to a European new
born (27). In general, South Asians have a lower birth weight
and are more insulin resistant than Europeans (28). Appa-
rently, low-birth-weight babies are highly likely to be subjected
to overfeeding, leading to neonatal weight gain, which might
substantially contribute toward the risk of diabetes later in life
(29).
Unusually, Asian Indian groups have high concentrations
of nonesterified fatty acids (NEFA) in plasma during fasting
despite relative hyperinsulinemia, and this concentration is not
suppressed by oral glucose administration (30). They also con-
comitantly have high plasma leptin and low plasma adiponec-
tin concentrations. Indians have higher levels of central obesity
(measured as waist circumference, waisthip ratio, visceral fat
mass, and posterior subcutaneous abdominal fat) (31). These
changes are independent of obesity or intra-abdominal fat dis-
tribution and therefore these abnormalities are further aggra-
vated with the development of obesity. The Indian thin-fat
phenotype is typically characterized by lower lean body mass
and a higher quantum of subcutaneous fat, which is associated
with an increased risk for cardiometabolic disease at any
given BMI, compared to Caucasians. Migrant Indians also have
greater insulin resistance than native local populations, which
relates to central obesity (measured as waisthip ratio, level of
visceral fat, central subcutaneous fat or body fat percentage).
A study (32) comprising middle-aged males in villages, urban
slums (usually the migrant rural population), and urban
middle-class in and around Pune in India showed substantial
correlation between body fat and insulin resistance. Despite
low BMI of 21, 34% of rural subjects had >25% of body fat
(the currently accepted definition of obesity). However, 45% of
first generation of rural migrants (represented by slum dwell-
ers) at a mean BMI of 22 had >25% body fat. Among the
middle-class residents who have been settled in cities for
many generations, at a mean BMI of 24, 84% of the population
had >25% body fat. Thus, there was a graded increase in insu-
lin resistance, type-2 diabetes, and other CVD risk factors dur-
ing a transition from rural to urban middle-class (32). This
indicates that the urban environment provides numerous
opportunities for the progression of cardiometabolic syndrome.
Pathogenesis of Diabetes Culminating
into Cardiovascular Disorders
Diabetes is known to involve complex cellular and molecular
mechanisms, leading to dysregulated glucose homeostasis in
the body. Insulin secretion and action are very tightly regu-
lated processes that maintain the physiologic glycemic levels.
Type-1 or insulin-dependent diabetes mellitus is basically
owing to autoimmune response-mediated destruction of the
508
IUBMB LIFE
pancreatic b-islets, resulting in insulin deficiency (33). Patients
with type-1 diabetes usually have to take exogenous insulin for
survival and for preventing the development of ketoacidosis.
Type-2 diabetes or noninsulin-dependent diabetes mellitus is
characterized by insulin resistance and is usually associated
with abnormal insulin secretion (33). Furthermore, the meta-
bolic changes in type-2 diabetes include impaired endothelial
function, subclinical inflammation, changes in adipokines, the
development of atherogenic dyslipidemia, increased levels of
free fatty acids (FFAs), and changes in thrombosis and
fibrinolysis.
Insulin Resistance
Insulin resistance is a major feature of type-2 diabetes and
develops in multiple organs, including skeletal muscle, liver,
adipose tissue, and heart. The insulin receptor is a tyrosine
kinase that is autoactivated by promoting the tyrosine phos-
phorylation on itself and on downstream signaling molecules
such as insulin receptor substrate family members IRS-1 and
IRS-2 (34). The IRS proteins become phosphorylated on serine
(and threonine) residues, probably by the action of multiple
kinases (35). Several other molecules in the insulin signaling
pathway (e.g., m-TOR and phosphatidylinositol 3-kinase) trans-
mit the activation signal downstream and also provide
upstream negative feedback signals (35). In addition, chronic
exposure of the cell to insulin may result in a diminished con-
centration of downstream elements, including key components
such as the IRS proteins (34,35).
As inadequate b-cell insulin secretion is fundamental to
the development of hyperglycemia in diabetes, insulin secre-
tion enhancers also play an important role in control of blood
glucose. Sulfonylurea derivatives act by closing pancreatic cell
potassium channels, which leads to enhanced secretion of
insulin (36). The mode of action of sulfonylurea derivatives
implies that they also act at low concentrations of plasma glu-
cose, which may cause hypoglycemia (36). Insulin therapy is
used in insulin-deficient patients who have poorly controlled
type-2 diabetes. Insulin acts primarily in muscle to overcome
insulin resistance, particularly when endogenous secretion of
insulin is reduced (37). However, the benefits of long-term
insulin therapy in patients at very early stages of type-2 diabe-
tes are unclear. Insulin does not directly reverse the patho-
physiological processes of this disease and most patients gain
weight or are at risk of hypoglycemia (38). If insulin therapy
manages insulin resistance in muscle, it also has the potential
to cause insulin-mediated nutrient toxic effects by promoting
excess glucose uptake during hyper lipidemic condition (gluco-
lipotoxic effects) (38).
Metformin is widely used to lower hepatic glucose
release, which decreases insulin resistance and plasma glu-
cose levels. Its action has been attributed to the activation
of AMP kinase (39). In one large study in patients with type-
2 diabetes, metformin therapy greatly lowered risk for major
coronary events (40). In addition, chronic inflammation has
been implicated in the pathophysiology of insulin resistance
Type-2 Diabetes
and type-2 diabetes, and NF-jB is crucial for upregulation
of proinflammatory signals. Salsalate is a nonacetylated form
of salicylate and is reported to target inflammation by inhib-
iting NF-jB (41). Recent studies have demonstrated that sal-
salates improved multiple metabolic measures in patients
with type-2 diabetes, including substantial reductions in fast-
ing and postprandial glucose, triglycerides, and FFAs
(41,42). The glucose-lowering effects of salsalates have been
partially attributed to NF-jB inhibition (41). Therefore, tar-
geting the inflammation using salsalate may improve glyce-
mic index, insulin resistance, and inflammatory profiles in
obese individuals who are at risk.
b-Cell Dysfunction
Pancreatic b-cell dysfunction is closely related with the initia-
tion and progression of both type-1 and type-2 diabetes (43).
In diabetic patients, pancreatic b-cell limits the glucose levels
by secreting excessive insulin to levels wherein the basal level
of insulin concentration may be raised to approximately dou-
ble the usual value. The defect in insulin release by b-cell is
the most crucial pathway, to look at crosstalk among type-2
diabetes, insulin resistance, and obesity. Diabetic patients
manifest decline in the number of b-cell as the latter undergo
rapid apoptosis. b-Cell mass was found to be decreased by
approximately 40 and 65% in lean and obese individuals,
respectively, in patients with type-2 diabetes, compared to
age- and BMI-matched nondiabetic individuals. Dysfunctioning
of b-cells leads to the secretion of specific markers like proin-
sulin along with amyloid fibrils which show pathogenesis of
their progressive destruction (44). Amyloid fibrils may be toxic
to islet cells, leading to b-cell apoptosis and even the islet cells
are then replaced by amyloid. This has been shown to be the
major pathway for b-cell loss in type-2 diabetes in Pima Indi-
ans who have amyloid infiltration of the pancreas at autopsy,
whereas few nondiabetic Pima Indians show the same patho-
logic change (44).
To protect b-cell function, the most effective therapeutic
strategy could be either to reduce the workload of b-cell or to
let b-cell rest. These two targets could be achieved by change
in lifestyle and/or reducing the obesity, and ultimately the use
of metformin (45). Lifestyle modification improves insulin sen-
sitivity and hence reduces b-cell work load (45). Metformin
also improves insulin sensitivity mainly through suppressing
hepatic glucose production (45). In addition, insulin therapy
has been shown to improve b-cell function probably through
inducing b-cell rest (37). It is likely that of pancreatic trans-
plantation to maintain long-term regulation of insulin and glu-
cose levels, such as the artificial pancreas, will ultimately
reduce the incidence and severity of diabetic complications.
However, the initial periods of poorly controlled diabetes can
have a prolonged damaging effect on the body, which may fur-
ther limit the subsequent protection that is provided to
improve glycemic control.
Pandey et al.
Obesity
The most critical factor in the emergence of metabolic diseases
is obesity that has drawn global attention. Individuals with
selective intra-abdominal or visceral adiposity are at substan-
tially higher risk for insulin resistance and metabolic syn-
drome, but the existence of visceral fat remains debated to be
either the cause or a biomarker of metabolic disease and
hence needs more investigation because not every obese
patient is insulin resistant or at high risk of diabetes and CVD
(46). According to the Nutrition Foundation of India, the preva-
lence of obesity is 1% for males and 4% for females in low
income groups, whereas for the middle socioeconomic class, it
was found to be 32.2% for males and 50% for females (47).
The Chennai Urban Population Study has revealed that the
abdominal obesity in the middle income population was 47.4
compared to 19.2% in the low income group (48).
Adipose tissues are known to be the source of a number of
metabolic hormones, cytokines, and other mediators such as
NEFA, glycerol, leptin and adiponectin, and various proinflam-
matory cytokines (49). Increased NEFA levels are observed in
obesity and type-2 diabetes, and are associated with the insulin
resistance (49,50). Increased intracellular NEFAs compete with
glucose for substrate oxidation, leading to the sequential inhibi-
tion of pyruvate dehydrogenase, phosphofructokinase, and hex-
okinase II activity (51). It was proposed that increased plasma-
FFA oxidation leads to an increase in the level of acetyl-
coenzyme A (acetyl-CoA) in mitochondria as well as in the ratios
of reduced/oxidized nicotinamide adenine dinucleotide (NADH/
NAD1), and hence attenuating pyruvate dehydrogenase activity.
This augments the intracellular citrate concentration, which in
turn inhibits phosphofructokinase, leading to an increase in
glucose-6-phosphate levels. The high levels of glucose-6-
phosphate subsequently inhibit hexokinase II activity and then
lead to decreased uptake of glucose. Thus, elevations in plasma
FFA levels in humans cause insulin resistance by initial inhibi-
tion of glucose transport and/or phosphorylation activity (52). It
has been proposed that increased NEFA delivery or decreased
intracellular metabolism of fatty acids results in an increase in
the intracellular content of fatty acid metabolites such as diacyl-
glycerol, fatty acyl-coenzyme A (fatty acyl-CoA), and ceramides,
which, in turn, activate a serine/threonine kinase cascade, lead-
ing to serine/threonine phosphorylation of IRS-1 and IRS-2, and
a reduced ability of these molecules to activated (51). Subse-
quently, events downstream of insulin-receptor signaling are
diminished. Pathways involving the induction of suppression of
cytokine signaling and the secretion of proinflammatory pro-
teins, such as tumor necrosis factor-a (TNF-a), interleukin-6 (IL-
6), or MCP-1 by adipocytes, endothelial cells, and monocytes,
increase macrophage recruitment and hence contribute to a
feed-forward process (53).
Atherogenic Dyslipidemia
Abnormal lipid metabolism, increased circulatory concentra-
tion, and elevated deposition of lipids in the skeletal muscle
are the major signs of insulin resistance and type-2 diabetes
509
 IUBMB LIFE

Pathophysiologic pathways contributing to type-2 diabetes and cardiovascular disease. The development and progression of
FIG 1 CVD involves complex interactions of the environment with the life course of an individual, incorporating fetal, early birth, and
adult components. A thin-fat phenotype may present at birth owing to genetic factors. Body weight and composition are
affected by maternal nutrition and well being. Gestational diabetes promotes transfer of metabolic maladaptations to the fetus.
Unhealthy diet, lifestyle, and environmental stress contribute toward abdominal obesity and insulin resistance ultimately lead-
ing to both glucose and lipid toxicity. The persistent impaired glucose intolerance culminates in type-2 diabetes and cardiovas-
cular disorder. Therefore, the prevention of type-2 diabetes must begin very early and continue throughout the life of an
individual.

(52). When plasma lipid level increases, it impairs insulin
activity. Increase in plasma FFA reduces insulin-stimulated
glucose uptake, whereas a decrease in lipid content improves
insulin activity in the skeletal muscle cells, adipocytes, and
liver (52,54). The excess FFA is ultimately stored in nonadi-
pose depots, leading to increased intramyocellular lipids,
which ultimately leads to insulin resistance (52,54).
Atherogenic dyslipidemia is a reliable predictor of cardio-
vascular risk and its pharmacological modulation reduces vas-
cular events in subjects with type-2 diabetes and metabolic
syndrome (55). Circulating FFA levels increase much before
the development of insulin resistance and other glycemic
abnormalities. Impaired insulin signaling further augments
lipolysis and disturbs the proper storage of fatty acids in adi-
pocytes (56). Once circulating FFA accumulates in the liver,
very low density lipoproteins are assembled and made soluble
by increased synthesis or post-translational stabilization of
Apo B (56). Thus, a lethal combination of excess delivery of
fatty acids and limited degradation of Apo B explains the
hypertriglyceridemia characteristic of insulin resistance.
FFAs bind with Toll-like receptor (TLR) activating NF-jB
through the degradation of the inhibitory complex IkBa by
IKKb-kinase (57). As a result, NF-jB triggers tissue inflamma-
tion owing to the upregulation of proinflammatory genes, that
is IL-6 and TNF-a. In addition, FetA, a liver-derived circulating
glycoprotein, has been shown to serve as an adaptor protein

510 Type-2 Diabetes

that directly links fatty acids to the activation of TLR4 (58).
Most convincingly, in vivo fatty acid infusion led to insulin
resistance in control mice, whereas FetA-knockdown mice
were protected from these effects. This hints at the exciting
possibility that targeting the FFAFetA-induced TLR-mediated
inflammation could have beneficial effects on improving glu-
cose homeostasis in T2D without affecting immune function
(58).
Abnormalities in all of the lipoprotein species seemingly
promote atherogenesis. At present, the crucial therapeutic tar-
get is to combat the increase in Apo B levels, which is corre-
lated strongly with low-density lipoprotein. The most impor-
tant therapeutic agents to treat elevated Apo B and/or
atherogenic dyslipidemia are 3-hydroxy-3-methylglutaryl coen-
zyme A reductase inhibitors (statins), cholesterol-absorption
blockers, bile-acid sequestrants, nicotinic acid, and PPARa
agonist (fibrates).
Metabolic surgery also seems to be a valuable treatment
option for selected patients with type-2 diabetes. The objective
of bariatric surgery is to decrease excess body weight and
hence to reduce related comorbidities. The several types of
metabolic surgery include gastroplasty, laparoscopic adjusta-
ble gastric bandinzg, sleeve gastrectomy, gastric bypass, and
biliopancreatic diversion (59). The results of a meta-analysis of
621 studies with 135, 246 patients showed that overall 78.1%
of patients with diabetes had resolution, and an additional
8.5% showed improved glycemic control (60). Although there
is no evidence available which suggests that metabolic surgery
confers long-term protection from vascular complications in
patients and therefore further research is needed before it is
accepted as a primary mode of treatment.
Conclusions
Type-2 diabetes is a rapidly increasing epidemic with a catas-
trophe of vascular complications worldwide, but the disease
prevention and management strategies are similar across the
most developing countries. The major lacunae in achieving
normal glucose levels among populations are the prevalence of
economic imbalance, inadequate health-care facilities, and
poor educational status in these countries. In addition, the dia-
betes prevention and management guidelines are mainly
designed on trials in western populations, and hence there is
no assurance whether these guidelines when implemented in
South Asia will be useful or not. Similarly, there is no random-
ized trial data available for the pan-India population. Despite
the increase in diabetes and CVDs, there remains a scarcity of
studies investigating the precise status of the disease because
of the geographical, socioeconomic, and ethnic nature of such
a large and diverse country. As the cardiometabolic disorders
are highly prevalent across all sections of society within India,
exhaustive research and interventions are required, at both
regional and national levels, to try to reduce the devastating
rise in diabetes that is predicted for the upcoming years. A
number of studies suggest that the quality of diabetes care is
Pandey et al.
suboptimal, whereas its cost is high especially in developing
countries. In fact, the lower economic groups suffer the most
as they spend 2534% of their income on diabetes care with
least hope. The challenges for diabetes care in Asian coun-
tries, especially in India, require mandatory education and
awareness to alert the population against the most common
risk factors for diabetes (Fig. 1). The patients may undergo
supervised training to manage their disease more effectively.
Furthermore, when in advanced stages, the treatment of car-
diometabolic disorders collectively requires polydrug therapy,
but even then the individual risk factors remain poorly con-
trolled in a majority of cases. As the primary goal of therapy is
to stall or delay the progression of metabolic deterioration,
therefore lifestyle therapy should be introduced early and
aggressively, and maintained at every stage of management.
This may be followed by drug management, which includes
the development of safe, effective, and simple drug regimens.
Thus, the prevention of diabetes and associated cardiometa-
bolic complications should be an essential agenda of public
health management authorities worldwide.
Acknowledgement
The authors sincerely acknowledge Sulagna Bhattacharya,
Regional Centre for Biotechnology, for carefully reading and
editing the manuscript.
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