Sweetness celebrated in our country with enthusiasm and our festivals have orchestrated its amalgamation with
celebration and tradition amidst profoundness.
obesity and Diabetes has paralyzed a large section of the countries population with petrifying consequences.
Matters have been made worse by the arduous effects they have exerted in sync highlighting their association.
They have proven to be mirror images of each other in the route of their manifestation and progression.
Obesity is defined as an accumulation of excessive fat where in enlargement of adipose tissue occurs and health
is impaired. The enlargement can be explained by two possible growth mechanisms that are, Hyperplasia Increase
in cell number and Hypertrophy- Increase in cell size.
Diabetes is characterized by abnormally high level of glucose in the blood resulting in hyperglycemic conditions.
This occurs because of the marked inability of the B-Langerhans islet cells of the pancreas to produce insulin.
Also the peripheral tissue show resistance in insulin uptake.
Diabetes has been classified into 2 categories.
Types of Diabetes
Type1 Diabetes (T1D)
It is an autoimmune diseases in which the antibodies of the immune system attacks and destroy the B-Langerhans
islet cells of pancreas. Hence there is an absolute deficiency of insulin secretion.
Type 2 Diabetes (T2D)
In this condition cells become insensitive to insulin and show resistance to insulin action. Thus leading to a
decrease in transport of glucose into the liver, muscle cells and fat cells, giving rise to hyperglycemic conditions.
Prevalence of these diseases have been shown in various age groups.
Diabetes has shown no clemency affecting children and adults of various age groups.
- Diabetes has engulfed 422 million people worldwide and has caused 4.6 million deaths every year. It is estimated
that by the year 2035, diabetes would be the 7 leading cause of mortality worldwide.
- TID can manifest itself at any age but mostly children between the age group 5 to 7 years or in puberty are affected.
- Globally Finland shows the most number of cases of T1D aggregating to more than 60 cases per 100'000 people every year.
- India has very low number of TID cases showing around 0.1 case per 100'000 people every year. T2D is prevalent
among adults with more than 65 million patients in India making it the diabetic capital of the world.
India is going under major epidemiological, nutritional and demographic changes owing to its rise in economy.
Hence these transitions have made obesity prevalent among kids and adults.
- There are 604 million obese people worldwide and has led to 2.6 million deaths every year.
- 30-45 million cases of obesity worldwide have been reported in children between the age group of 5-17 years.
- These figures look staggering in the 22 million cases that have been reported in kids below the age of 5 years.
- India is no stranger to obesity as upto 8% (2%-8%) of school going children and 280 million adults have been reported.
- Obesity is a major risk factor for developing diabetes and hence these figures are a mere reflection of the conditions
that may exists among the individuals worldwide.
A Lifestyle Disorder
One of the driving force behind the high prevalence of diabetes is the rise of obesity. These disorders in combination
have exerted their presence because of the sedentary lifestyle along with dietary factors and lack of physical activity.
Energy imbalance as seen in these conditions occurs when energy intake exceeds the energy expenditure. In-turn the
body witnesses a sharp rise in weight as adipocytes store these excess triglycerides leaning towards obesity and risk
of developing diabetes. Diet which contains high energy foods is strongly obesogenic and these include saturated and
trans fatty acids found in fast foods. However, there are exceptions with foods like nuts and olive oil which are energy
dense but, do not increase weight when added to diet. Consumption of sugar sweetened beverages have had a greater
impact in weight gain, and further contribute to the energy imbalance in the body. A common conundrum in modern
lifestyle occurs through sleep deprivation. Thus altering the function of glucose metabolism and again leading to decreased
insulin sensitivity and glucose tolerance.
Obesity further accelerates diabetes causing
Diabesity
A majority of individuals with diabetes are obese hence there exist a strong unification between obesity and diabetes.
This led to the term 'Diabesity' suggesting a pathophysiological link between the two.
Linking Mechanism
The Inflammation Hypothesis, Lipid Overflow Hypothesis and Adipokine Hypothesis as under have explained the
association of obesity with diabetes upto a greater extent. Although there are several in-vivo studies with promising
outcomes, further studies are yet required to link obesity with T1D via these mechanisms.
Inflammation Hypothesis
Inflammatory process marks an obese individual to develop insulin resistance as there is production of proinflammatory
cytokines in the excessive adipose tissue stored in both conditions. Hence the term metaflammation was coined to describe
this chronic inflammation by metabolic cells in response to excess nutrients and energy. This hypothesis suggests that
macrophages from blood circulation accumulate in the adipose tissue. So these adipose tissue macrophages that
accumulate during diet induced obesity cause inflammation and mediate insulin resistance in adipocytes. The inflammation
is mediated by Macrophage Migration Inhibitory Factor (MIF), a chemokine like inflammatory regulator directly associated
with the degree of insulin resistance. Adipose tissue macrophages serve as a major reservoir for proinflammatory molecules
and these cytokines function in the progression of this reaction.
The major molecules that take part in this reaction are
- TNF-a (Tumor Necrosis Factor-a)
- Monocyte chemotactic protein-1 (MCP-1)
- Toll-Like Receptor-4
- Interlukin-1
TNF-a
TNF-a is a cytokine produced by the macrophages and their levels have been found to be elevated in obesity and diabetes.
It has been reported that it suppresses the process of lipogenesis and partly block the intra cellular signaling from the
insulin receptor causing elevated levels of glucose in the blood. Intracellular concentration of ceramides, a major lipid
constituent of epidermal cells increases because of TNF-a. DNA fragmentation and apoptosis are the basic functions
of ceramides but in skeletal muscles they along with diacylglycerols activate serine kinases that disrupt the insulin
signaling cascade and lower insulin sensitivity. Further they induce apoptosis in B-cells.
Monocyte chemotactic protein-1 (MCP-1)
The proinflammatory chemokine Monocyte Chemotactic Protein-1 (MCP-1) attracts leukocytes to inflamed sites.
Insulin induces expression and secretion of MCP-1 in insulin resistant adipocytes. This protein inturn causes dedifferentiation
of adipocytes and cause hyperinsulinemia and obesity, including T2D as there is infiltration of macrophages in the
adipose tissue.
Toll-Like Receptor-4
They are membrane spanning receptors that are thought to play an important role in fatty acid induced insulin
resistance. They have been shown to be expressed on adipocytes and get activated by Lipopolysaccharides (LPS).
Dietary saturated fatty acids have shown to activate this receptor and up regulate MCP-1 levels in the adipose
tissue causing inflammation and promoting progression towards diabetes.
Interleukin-1 (IL-1)
The inflammatory response is mediated by macrophages via releasing IL-1, and it depends on the free fatty acid
content as seen in obese individuals.
Lipid Overflow Hypothesis
Healthy adipose tissue in non-obese people has the ability to expand and store excessive nutrients but have failed
to exhibit this feature in obese individuals. Hence after adipose tissue reaches its limit and fails to expand further
the lipids then overflow to other perepheral tissues in the skeletal muscle, liver and pancreas. Subcutaneous Adipose
Tissue (SAT) is a major storage depot for excessive lipid molecules. SAT expands via hypertrophic response leading
to insulin resistance. Also ectopic fat, that is deposition of triglycerides in nonadipose tissue cells causing lipotoxicity,
has shown to have a direct link to T2D. A forced process of deposition of fats in such tissues has caused accumulation
of lipid metabolites that inhibits the insulin signaling pathway. Hence, lipotoxicity along with the molecular action of
ceramides and DAG has proven to be major ruling factors to develop insulin resistance in obese individuals.
The process of Fatty Acid (FA) metabolism in skeletal muscle is regulated at multiple sites. In the oxidation of Long
Chain FA (LCFA) lipolysis, LCFA gets released from adipose tissue and the Free Fatty Acid is delivered to the skeletal
muscles for oxidation. However in obese conditions this process is affected leading to accumulation of fatty acids
and thus enhanced level of triglycerides, DAG and ceramides results in impairment of insulin signaling. This occurs
through increased serine phosphorylation of the insulin receptor and the insulin receptor substrate 1 by Protein
kinase C (PKC). Also the reduced levels of enzymes like citrate synthase and B-hydroxyacyl dehydrogenase that are
involved in fatty acid oxidation explains the mechanism of linking obesity with diabetes.
Adipokine Hypothesis
Along with the storage of triglycerides adipose tissue also secretes wide range of adipokines such as the TNFa,
IL-1, MCP-1 and Leptin are involved in Inflammatory responses. With rise in volume of adipose tissue in obesity
there is increased secretion of these molecules in circulation and thus play its role in insulin resistance.
Leptin functions by demoting food intake and promoting energy expenditure signaling through the central nervous
system. Any mutations in the leptin gene or receptor has led to obesity. Leptin plays a vital role to increase insulin
sensitivity by maintaining glucose homeostasis and by decreasing the intracellular lipid accumulation hence
avoids lipotoxicity.
Diagnostic Methods for Obesity and Diabetes
Obesity in a individual can be found using the following tests
- Body Mass Index (BMI) test- A value of 30 kg/m or more classifies as obesity. However a greater risk of
mortality exist among T2D patients with the BMI value of 28 kg/m or more.
- FSH test- High levels of FSH test may be responsible for fat accumulation both in men and women causing obesity.
- Luteinizing Hormone (LH) test. It is required for normal functioning of male and female reproductive system
and high levels of LH can cause obesity.
Diabetes can be diagnosed by the following tests
- Blood glucose test: Most widely used test to detect diabetes. It includes random blood sugar, fasting blood sugar, and post prandial blood sugar levels.
- Hba1c test: HbA1C forms a useful biomarker, for detection of pre-diabetic conditions and also acconts for a patients history with this disorder for the past 90-120 days.
- fructosamine test: Fructosamine particularly beneficial for anemic patients and pregnant women and reveals the record of the last 14-21 days of the patient.
- blood ketone test: Body produces ketones incase of decreased Insulin sensitivity and hence detection of these
ketone bodies can help with diagnosis of diabetes.
General approaches to counter these conditions
Weight loss and diet are primary targets for managing these conditions. Hence only a guided approach can be beneficial
and eliminate any risk associated with change in diet. An approach in a 6 month period span to loose 10% body weight
with anywhere between 500 grams to a kilogram per week is considered safe.
Physical activities to reach this goal requires a moderate workout of 30 mins or more per day with a steady increase
to ensure all norms on safety are met.
A daily intake of minimum 1600 kcal and 1200 kcal for men and women respectively will ensure proper nutrition and
nourishment.
So with ever increasing patient number diabetes and obesity have spread their wings across the length and breadth
of this country, commanding immediate attention to diagnosis and care.
