Health Hamesha

Diagnostic tests

Self Monitoring Test
1. Extremely useful for outpatient monitoring specially for patients who need tight control for their glycemic state.
2. A portable battery operated device that measures the color intensity produced from adding a drop of blood to a glucose oxidase paper strip.
3. e.g. One Touch, Accu-Chek, DEX, Prestige and Precision.
Laboratory tests
1. Glucosuria
  - To detect glucose in urine by a paper strip
  - Semi-quantitative
  - Normal kidney threshold for glucose is essential
2. Ketonuria
  - Semi-quantitative
3. Fasting blood glucose
  - Glucose blood concentration in samples obtained after at least 8 hours of the last meal
4. Random Blood glucose
  - Glucose blood concentration in samples obtained at any time regardless the time of the last meal
5. Glycosylated hemoglobin (HbA1C)
  - HbA1C is formed by condensation of glucose with free amino groups of the globin component of hemoglobin
  - Normally it comprises 4-6% of the total hemoglobin.
  - Increase in the glucose blood concentration increases the glycated hemoglobin fraction.
  - HbA1C reflects the glycemic state during the preceding 8-12 weeks.
6. Serum Fructosamine
  - Formed by glycosylation of serum protein (mainly albumin)
  - Since serum albumin has shorter half life than hemoglobin, serum fructosamine reflects the glycemic state in the preceding 2 weeks
  - Normal is 1.5 - 2.4 mmole/L when serum albumin is 5 gm/dL.
Oral Glucose Tolerance Test (OGTT)
- 75 g glucose load taken in the morning after an 8-10 hour non-caloric fast.
- blood glucose levels are taken in the fasting state and at 1 and 2 hours after drinking the glucose.
- Various factors might affect the reliability of the test:
  - Avoidance of carbohydrate over several days reduces the first-phase insulin response to glucose. It also results in a delayed second-phase response, increasing the risk of a false positive OGTT result. Therefore, people should be asked to eat their normal carbohydrate load during the days leading up to the test
  - Glucose tolerance changes throughout the 24-hour period
  - Glucose tolerance is also affected by illness; therefore OGTT should be performed in the morning, only in people who are well
  - People should rest throughout the test in a semi-reclined position and not breastfeed; both exercise and breastfeeding will increase glucose disposal

Advice by Health Hamesha on periodic monitoring to know status of diabetes and hypertension control for better disease management.

It recommends specific interventions for periodic medical assessment, laboratory tests and education to guide affective patient self-management.

KEY COMPONENTS	RECOMMENDATION AND LEVEL OF EVIDENCE	FREQUENCY
PERIODIC ASSESSMENT	Assessment should include blood pressure, height, weight, BMI Assess cardiovascular risks (smoking, hypertension, dyslipidaemia, sedentary lifestyle, obesity, stress, family history, age > 40) Comprehensive foot exam (visual, monofilament, and pulses) Screen for depression Dilated eye exam by ophthalmologist or optometrist or if no prior retinopathy, may screen with fundal photography.	Annual comprehensive foot exam Record BP at every visit Yearly dilated eye exam
LABORATORY TESTS	Tests should include: A1C Urine micro albumin measurement Serum creatinine and calculated GFR Lipid profile, preferably fasting Consider TSH and LFTs	A1C every 3-6 months Other tests annually: urine micro albumin , albumin-to-creatinine ratio
MEDICAL RECOMMENDATIONS	Care should focus on smoking, hypertension, lipids and glycaemic control: Medications for tobacco dependence unless contraindicated Treatment of hypertension using up to 3-4 anti-hypertensive medications to achieve adult target of < 140/90 mmHg	At each visit until therapeutic goals are achieved

Periodic monitoring of complications

Complication	Tests	Frequency
Hypertension	BP taken with appropriate size cuff using optimal technique.	Every visit.
Blood glucose control	HbA1c	Every 3 months until the target level is reached; thereafter, patients should be monitored at least every 12 months.
Foot ulcers	Physical exam focused on ankle reflexes, dorsalis pedis pulse, vibratory sensation, and 5.07 monofilament touch sensation performed by a provider qualified to determine the level of risk for foot ulcers.	Patients at very high risk should be seen every months by a wound care nurse. Patients at increased risk and average risk should be screened annually.
Microalbuminuria	Micro albumin/creatinine ratio.	Annually.
Hyperlipidaemia	Fasting LDL.	Annually.
Retinopathy	Dilated eye exam by a trained eye services professional or Non-dilated digital photography followed by a comprehensive exam for those who test positive.	Patients with evidence of retinopathy should be screened annually Patients without evidence of retinopathy should be screened every 2 years.
Electrolyte and chemistry abnormalities	Serum creatinine and Serum potassium.	At least annually.

References

Cooprative, G., 2015. Type 2 Diabetes Screening and Treatment Guideline. Group Health, (June), pp.1–17.

Criteria for diagnosis

Note: ** confirmation of the diagnosis depends on repeated values done on another day, unless unequivocal hyperglycaemia and metabolic decompensation are present.

Target Values
	mg/dl	mmol/l
Fasting Glucose	80-110	4.5 - 6.1
2 hours postprandial	120-140	6.7 - 7.8
Glycosylated hemoglobin (HbA1c)(normal range 4-7)	<7.5	< 7.5
Blood pressure (mm/Hg)	<130/85	< 130/85
Total Cholesterol	< 180	< 4.66
HDL-Cholesterol (males)	> 40	>1.03
HDL-Cholesterol (females)	> 50	>1.3
LDL-Cholesterol	< 100	<2.6
Triglycerides	< 150	< 1.7

Metabolic syndrome

The metabolic syndrome is a cluster of risk factors which predispose a person to Type 2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular disease (ASCVD). Its presence confers a two fold increase in the risk for major CVD events and a five fold increase in the life time risk for T2DM.
Once a person is diagnosed to have diabetes, he or she must be thoroughly investigated for the presenceof other components of the Metabolic Syndrome, such as hypertension, lipid abnormalities, weight characteristics, especially central obesity, presence of cardiovascular disease, novel risk factors and for the presence of the long term diabetic complications.

IDF clinical criteria for metabolic syndrome
Measure (central obesity sine qua non plus any two of four other criteria constitute a diagnosis of metabolic syndrome)	Categorical cut points
Central obesity	Waist circumference ethnic specific ( 80 cm for women) for Indian subjects
Raised triglycerides	>150 mg/dl (1.7 mmol/l) or on specific treatment for this lipid disorder
Reduced HDL cholesterol	<40 mg/dl (1.0 mmol/l) in men, <50 mg/dl (1.3 mmol/l) in women or on specific treatment for reduced HDL-C
Raised blood pressure	< 130 mmHg systolic blood pressure or 85 mmHg diastolic blood pressure or on treatment for previously diagnosed hypertension
Elevated fasting plasma glucose	Fasting plasma glucose 100 mg/dl (5.6 mmol/l) or on treatment for previously diagnosed type 2 diabetes

Screening for Asymptomatic individuals

Age ≥ 30 yrs
Over weight – Body Mass Index ≥ 23 kg/m2
Central obesity – Waist Hip Ratio men > 0.90, women > 0.85
Family history of diabetes
Sedentary life style
Previously identified Impaired Fasting Glucose (IFG) or Impaird Glucose Tolerance.
History of gestational diabetes mellitus (GDM), recurrent fetal loss or delivary of large baby ≥ 3.5 kg
Hypertension ( > 140/90 mmHg in adults)
Dyslipidemia

Screening of GDM

Screening at the first visit has become important as the prevalence of type 2 diabetes has increased in the younger population. Many women may not be aware they have type 2 diabetes when they become pregnant.
It is recommended that screening all women for GDM at 24-28 weeks gestation.
Diagnosis based on a 75 gm glucose load given in fasting state
GDM diagnosed when one or more of the following is present:
- Fasting 92 - 125 mg/dl (5.0 – 6.9 mmol/L)
- 1 hour post 75 gm load >180 mg/dl (10 mmol/L)
- 2 hour post 75 gm load >153mg/dl (8.5 mmol/L)
If woman tests negative, screening at 32 weeks also may be necessary in presence of high risks.

Management of diabetes

Managing your diabetes is not a science. It is an art.

The aims of diabetes management are to achieve and maintain ideal body weight, euglycaemia and desirable lipid profile, prevent and postpone complications related to diabetes.
This can be intervened by following measures:
- Weight Optimization
- Healthy diet
- Exercise
- Anti-hyperglycemmic therapy
Lifestyle modifications are the cornerstone of management of diabetes mellitus and includes the prescription of a healthy diet, regular exercise, management of stress and avoidance of tobacco.
This can be achieved by maintaing ideal anthropometric measurements, includes:
- Body weight
- Height
- BMI
- waist circumference

Body Mass Index (BMI)

BMI helps to define overweight and obesity using standard nomograms
Weight and height measurements are used to calculate Body Mass Index (BMI) – also known as the Quetelet Index.

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Body shape has been found to be important when predicting a person’s risk of cardiovascular disease and metabolic conditions. Abdominal fat is an important risk marker for cardiovascular disease and type 2 diabetes.
People may be considered to be at high risk when the WHR is ≥0.9 cm in men and ≥0.8 cm in women.
The waist-to-hip ratio (WHR) can be used to identify people as either pear- or apple-shaped. People with a pear-shaped body have a low WHR and are at a lower risk from cardiovascular complications, compared to people with an apple-shaped body.

	Men	Women
Waist hip ratio	≥ 0.9 cm	≥ 0.8 cm
Waist circumference (measurements indicate central adiposity)
Europid, Sub Saharan Africans, Eastern Mediterranean and Middle Eastern Populations	≥ 94 cm	≥ 80 cm
South Asians, Chinese, Japanese, Ethnic South and Central Americans	≥ 90 cm	≥ 80 cm

Diet

ensuring weight control
providing nutritional requirements
allowing good glycaemic control with blood glucose levels as close to normal as possible
correcting any associated blood lipid abnormalities
Dietary recommendations should be individualized according to persons ethnicity, cultural, family background, personal preferences and associated co-morbid conditions. It should be flexible in variety and preparations of food choices and timing of meals according to the persons daily routine.

Dietary fat should provide 25-35% of total intake of calories but saturated fat intake should not exceed 10% of total energy. Cholesterol consumption should be restricted and limited to 300 mg or less daily.
Protein intake can range between 10-15% total energy (0.8-1 g/kg of desirable body weight). Requirements increase for children and during pregnancy. Protein should be derived from both animal and vegetable sources.
Carbohydrates provide 50-60% of total caloric content of the diet. Carbohydrates should be complex and high in fibre.
Excessive salt intake is to be avoided. It should be particularly restricted in people with hypertension and those with nephropathy.

Click here to open the diet chart

Exercise

An increase in physical activity is an important part of your weight management program. Most weight loss occurs because of decreased caloric intake.
Sustained physical activity is most helpful in the prevention of weight regain. In addition, exercise has a benefit of reducing risks of cardiovascular disease and diabetes, beyond that produced by weight reduction alone.
Starts exercising slowly and gradually increase the intensity. Trying too hard at first can lead to injury.
Brisk walk for 30-60 min or its equivalent to physical activity.
An exercise schedule should be one that the individual enjoy and which suits his/her needs.

Aerobic Exercise: Aerobic means “using oxygen for energy”.
- use large muscles (legs, shoulders, chest, and arms)
- can be performed continuously
- burns calories and is critical to losing fat and keeping it off.
Isometric exercises, such as weight lifting, etc., are not recommended for most patients although they warrant consideration when total skeletal muscle mass needs to be increased.
Resistance Training
- helps in increasing the number of Insulin receptors
- Improves sensitivity of insulin receptors in skeletal muscle
- maintains muscle while losing fat.
- Upper arm resistance training shown to lower blood glucose

References MISRA R. Indian Foods: AAPI’s Guide To Nutrition, Health and Diabetes. 2nd ed. Chennai: Allied Publishers Private Limited; 2016.

Frequency and duration
Intensity
- The intensity of the exercise needs to be individualised.
- For most patients, exercise should be initiated slowly, and the intensity should be increased gradually. The exercise can be done all at one time or intermittently over the day. Initial activities may be walking or swimming at a slow pace. The patient can start by walking 30 minutes for 3 days a week and can build to 60 minutes of more intense walking at least 5 days a week, preferably daily. Before more strenuous exercise, a warm-up period of 5 minutes of stretching and other gentle activity is advised, as is a final cool-down period of progressively decreasing vigor.
- The intensity of the exercise should be increased gradually.
- Intensity is usually measured in terms of the percentage of the patients maximum heart rate (MHR). Initial exercise should be at a reduced intensity which should be at a reduced intensity which should then be increased to reach about 60-70% of the MHR. (MHR = 220 - age of the patient).
- Limiting the intensity of the exercise such that the systolic blood pressure does not exceed 180 mm Hg would seem prudent.
- Any patient undergoing an exercise program, who complains of any signs or symptoms which would have contraindicated such a program initially, should discontinue the program, and have a detailed re-evaluation before restarting the exercise regimen.

Examples of moderate amounts of physical activity
Common Chores	Sporting Activities
Washing and waxing a car for 45-60 minutes	Playing volleyball for 45-60 minutes
Washing windows or floors for 45-60 minutes	Playing touch football for 45 minutes
Gardening for 30-45 minutes	Walking 13/4 miles in 35 minute (20min/mile)
Wheeling self in wheelchair 30-40 minutes	Basketball (shooting baskets) 30 minutes
Pushing a stroller 1½ miles in 30 minutes	Bicycling 5 miles in 30 minutes
Raking leaves for 30 minutes	Dancing fast (social) for 30 minutes
Walking 2 miles in 30 minutes (15min/mile)	Water aerobics for 30 minutes
Shoveling snow for 15 minutes	Swimming Laps for 20 minutes
Stair walking for 15 minutes	Basketball (playing game) for 15-20 minutes
	Bicycling 4 miles in 15 minutes
	Jumping rope for 15 minutes
	Running 1½ miles in 15 min. (10min/mile)

Exercise in GDM

Studies show that pre-pregnancy exercise helps to prevent GDM during pregnancy.
Any activity has more benefit than no physical activity in prevention of GDM.
- Start with light to moderate exercise, i.e. 10 minute walk after meals, upper body exercises while seated
- 30 minutes a day total is recommended.
Medical contraindications for exercise in pregnancy
- Haemodynamically significant heart disease, eg. Mod-severe valvular heart disease, cardiomyopathy, cyanotic heart disease
- Restrictive lung disease
- Preclampsia
- Incompetent cervix/ cerclage
- Multiple gestation at risk for premature labour
- Persistent second or third trimester bleeding
- Placenta praevia after 26 weeks gestation
- Ruptured membranes
Relative contraindications for exercise in pregnancy
- Severe anaemia
- Unevaluated cardiac arrhythmia
- Chronic bronchitis
- Poorly controlled type 1 diabetes
- Extreme morbid obesity (BMI > 40)
- Extreme Underweight (BMI< 12)
- Exercise in multiple gestation should be supervised
- History of extreme sedentary lifestyle
- Poorly controlled hypertension
- Orthopedic limitations
- Poorly controlled seizure disorder
- Poorly controlled hyperthyroidism
- Heavy smoker
- Intrauterine growth restriction in current pregnancy

References

Metzger BE, Buchanan TA, Coustan DR, De Leiva A, Hadden DR, Hod M. Summary and recommendations of the fifth international workshop-conference on gestational diabetes mellitus, Diabetes Care. 2007; 30(suppl 2):S251-260.
Harris, GD, White, RD. Diabetes management and exercise in pregnant patients with diabetes. Clinical Diabetes. 2005;23(4):165-168

Anti – hyperglycemic therapy

Oral Hypoglycemic agents (OHA) therapy
- Sulfonylurea
- Biguanides
- Meglitinides
- Thiazolidinediones Glitazones
- α-Glucosidase inhibitors
Insulin
- Insulin Aspart
- Lispro
- Glargine
- Ultralente
- Lente
- NPH

Consider therapeutic life style changes (TLC) for all patients with Type 2 DM
Initiation of therapy may depend on the level of HbA1C
- HbA1C < 7% may benefit from TLC
- HbA1C 8-9% may require one oral agent
- HbA1C > 9-10% my require more than one oral agent

Oral Agents commonly used in the Treatment of Type 2 Diabetes

Agent	Dose	Duration of action	Efficacy	Major side effects	Contraindications
Sulfonylureas Increase insulin secretion by pancreas; Metabolizedprimarily liver, excreted by kidney			Average decrease in FPG 60-80 mg% Average decrease in HbA1c: 0.8- 2%	Hypoglycemia; abdominal discomfort, nausea in around 1% to 3% patients; hyperacidity, metallic taste or change in taste; weight gain;	Significant renal or hepatic dysfunction
Glipizide	2.5-20 mg/day	8-12 hours		Hypoglycemia risk 4-6%
Glibenclamide	2.5-20 mg/day	16-24 hours		Hypoglycemia risk 4-6%
Gliclazide	80-240mg/day	6-8 hours		Hypoglycemia risk < 2%
Glimepiride	1-8 mg/day	24 hours		Hypoglycemia risk < 2%
Biguanides Decreases hepatic glucose production Not metabolized, eliminated by kidneys			Average decrease in FPG 65-75 mg% Average decrease in HbA1c: 1 - 2%	Gastrointestinal discomfort, especially nausea; metallic taste in mouth, loss of appetite; vitamin B12 deficiency, rarely lactic acidosis; weight loss	DKA, alcoholism, renal or hepatic dysfunction; congestive heart failure; acute illness; cardiovascular collapse (shock); acute myocardial infarction;septicemia; acute or chronic metabolic acidosis; respiratory insufficiency;
Metformin	500-1500 mg/ per day with meals	8 hours
Alpha-glucosidase inhibitors Delays absorption of complex carbohydrates in intestinesNot absorbed systemically	To be taken with first bite of the meal		Average decrease in FPG 25-30 mg% Average decrease in HbA1c: 0.5 to1%	Abdominal discomfort, bloating, "gas" formation, nausea and diarrhea;	liver disease, bowel or intestinal disease, intestinal obstruction
Acarbose	25-100 mg with each meal	4 Hours
Miglitol	50-100mg. with each meal	4 Hours
Voglibose	200mg with each meal
Meglitinides Increases pancreatic insulin secretion Metabolized in the liver			Average decrease in FPG 30-40 mg% Average decrease in HbA1c: 0.5 to 0.7%	Average decrease in FPG 30-40 mg% Average decrease in HbA1c: 0.5 to 0.7% Hypoglycemia; gastrointestinal upsets; muscle aches, URTI and flu-like symptoms; body ache;	Type 1 DM; diabetic ketoacidosis, hepatic dysfuntion
Repaglinide	0.5-4 mg with each meal	3 hours
Nateglinide	60-120 mg with each meal	3 hours
Glitazones Reduces insulin resistance at cellular level; Metabolized in the liver	Taken with or without food		Average decrease in FPG 70-80 mg% Average decrease in HbA1c: 1.5 - 2.5 %	Weight gain, edema;URTI; toothaches; sore throat; body ache; headaches	Hepatic dysfunction; CHF, increasing edema
Rosiglitazone	4-8 mg/day	12 hours
Pioglitazone	15-45 mg/day	24 hours
Incretin mimetics Inhibit peptide hormone metabolism by DPP-IV enzyme, thus a) enhance insulin secretion; b) inhibit glucagon secretion; c) improve ß-cell function	Oral
Sitagliptin	100mg/day can be taken with or without food.		More dominant effect on postprandial levels, although some effect on fasting levels also seen	Diarrhea; gas; headache; indigestion; nausea; sore throat; stomach upset; stuffy or runny nose; vomiting; weakness.anorexia and early satiety are notable;	Need for dosage adjustment based upon renal function; Avoid if possible in patients using digoxin

OHA THERAPY in a non-obese Type 2 Diabetes patient

OHA THERAPY in a overweight (obese) Type 2 Diabetes patient

References

Diabetes India - Site Consensus diabetes [Internet]. Diabetesindia.com. 2016 [cited 20 October 2016]. Available from: http://www.diabetesindia.com/diabetes/cons_oral_agents.html

ANTI-HYPERGLYCEMIC THERAPY

Therapeutic options: Insulins

The use of insulin therapy is often required to achieve optimal blood glucose control.
In most Type 2 Diabetes Mellitus T2DM patients this should be accompanied by using insulin sensitizers, which would lower the insulin resistance seen in the patients with T2DM and allow a much smoother control at the minimal possible dosages.

Type+(Trade Name)	Onset of Action	Peak	Duration	Nursing Intervention	Adverse effects	Treatment
Rapid-acting (Clear) Insulin Lispro (Humalog) Insulin Aspart (Novorapid) Apidra (insulin glulisine)	10-15min	60-90min	4-5hrs	Take within 15 min before meals or within 20 min after meals	Hypoglycemia Skin rash at injection site Lipodystrophies (increase in fat mass) at injection site	Patients should be aware of symptoms of hypoglycemia Oral administration of 10-15 gm glucose IV dextrose in patients with lost consciousness 1 gm glucagon IM if IV access is not available Use more purified insulin preparation rotate the site of injection
Short Acting/Regular Insulin (clear) Humulin R	30-60	2-4hrs	5-8hrs	Take 30 min before meals
Intermediate-acting (cloudy) (NPH/Lente)	1-4hrs	4-12hrs	18-24hrs	Take 30 min before meals. Covers insulin needs half of the day or overnight
Ultra Lente and Glargine (clear)	4-8hrs	18hrs	24-38hrs	Note: Glargine can not be mixed with any other insulin
Premixed: 10/90, 20/80, 30/70, 40/60, 50/50 (cloudy)				ideal time to give patients with their premixed is 30 min before their meal, with their meal and after their meal Drawing up Insulin: Clear then cloudy to avoid contaminating the clear insulin

Methods of Insulin Administration

Insulin delivery methods
- Ordinary SQ injection
- Insulin pen
  - preloaded with insulin; “dial” the dose
- Insulin pump
  - Continuous “basal” infusion. At mealtime, user programs to deliver “bolus” infusion that correlates with amount of CHOs ingested. Allows tight control and greater flexibility with meals and activity
Example of algorithm for insulin administration

	Breakfast	Lunch	Supper	Bedtime
Usual Dose (Example)	Rapid 10	Rapid 8	Rapid 12	Long acting Analogue 24
If blood glucose is …	Units of insulin reduced (-) or added (+) to usual dose
≤4 (72)	- 5 units	-4 units	-6 units	continue
4.1-6.0 (73-108)	-2 units	-2 units	-2 units
6.1-10.0 (109-180)	Usual dose	Usual dose	Usual dose
10.1-12.0 (181-216)	+2 units	+2 units	+2 units
12.1-14.0 (217-252)	+4 units	+4 units	+4 units
14.1-18.0 (253-324)	+6 units	+6 units	+10 units
≥18.1 (325)	+10 units	+8 units	+12 units

Insulin treatment scheme

Insulin premixed regimen

* Rosiglitazone should not be used along with insulin and the dose of pioglitazone should not exceed 30mg/day.

References

Diabetes India - Site Consensus diabetes [Internet]. Diabetesindia.com. 2016 [cited 20 October 2016]. Available from: http://www.diabetesindia.com/diabetes/cons_insulin_therapy.html

Diabetic complications

People with diabetes have an increased risk of developing a number of serious health problems. Consistently high blood glucose levels can lead to serious diseases affecting the heart and blood vessels, eyes, kidneys, nerves and teeth. In addition, people with diabetes also have a higher risk of developing infections.
Hyperglycemia causes acute reversible and cumulative irreversible changes which results in the:
- Increased production of free radicals
- Increased activity of polyol pathway
- Modified protein kinase C activity
- Early glycation products

Development of advanced glycation end products (AGE)

AGEs are a heterogenous group of molecules formed from the non-enzymatic reaction of reducing sugars with free amino groups of proteins, lipids and nucleic acids
AGE molecules (free, as peptides or protein-bound) are found in plasma, cells, and tissues and accumulate in the arterial wall, the kidney mesangium, and glomerular and other basement membranes.
Hyperglycaemia results in higher cellular glucose levels in those cells unable to reduce glucose intake e.g endothelial cells
This in turn results in increased levels of reduced nicotinamide adenine dinucleotide (NADH) and FADH, and results in mitochondrial production of reactive oxygen species (ROS), activating the Poly(ADP) Ribose Polymerase-1 enzyme (PARP1) by damaging DNA.
PARP1 in turn induce ADP-ribosylation of GAPDH causing its activation and subsequent accumulation of metabolites that activates multiple pathogenic mechanisms, one of which includes increased production of AGEs.
Effects of advanced glycation end products (AGE)
- Crosslinking of extracellular proteins
- Interactions with specific AGE receptors
- Crosslinking with intracellular DNA

AGE-induced Diabetes Mellitus complications

A large body of evidence suggests that AGEs are important pathogenetic mediators of almost all diabetic complications conventionally grouped into micro- and macroangiopathies via the formation of cross-links between molecules in the basement membrane of extracellular matrices of vascular/connective tissues and the engagement of RAGE resulting in adverse modification of the actions of hormones, cytokines and free radicals (Brownlee, 2005).
They include :

Diabetic retinopathy

Although people with diabetes are at increased risk for the development of cataracts and glaucoma, retinopathy is the most common pattern of eye disease.
Diabetic retinopathy is characterized by abnormal retinal vascular permeability, microaneurysm formation, neovascularization and associated hemorrhage, scarring, and retinal detachment.
Because of the risk of retinopathy, it is important that people with diabetes have regular dilated eye examinations. Some people develop a condition called macular edema. It occurs when the damaged blood vessels leak fluid and lipids onto the macula, the part of the retina that lets us see detail. The fluid makes the macula swell, which blurs vision.

Risk Factor

poor glycemic control,
elevated blood pressure,
hyperlipidemia.
long duration of diabetes
Pregnancy
presence of microalbuminuria, hypertension and smoking.

References

Jorge, R., Costa, R.A., Calucci, D., Cintra, L.P., Scott, I.U. (2006). Intravitreal Bevacizumab (Avastin) for Persistent New Vessels in Diabetic Retinopathy (Ibepe Study). Retina, 26(9), 1006-1013.
Elman M, Aiello L, Beck R, et al. Randomized trial evaluating ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology. 27 April 2010

Stages of retinopathy

Mild, nonproliferative retinopathy characterized by increased vascular permeability;
Moderate and severe nonproliferative diabetic retinopathy (NPDR), characterized by vascular closure;
Proliferative diabetic retinopathy (PDR), characterized by the growth of newblood vessels on the retina and posterior surface of the vitreous.
Macular edema, characterized by retinal thickening from leaky blood vessels, can develop at all stages of retinopathy.

Signs and symptoms

There are usually no symptoms in the early stages of diabetic retinopathy. Vision may not change until the disease becomes severe. This is why regular examinations for people with diabetes are so important.
vision becomes blurry;
trouble reading signs or books;
see double;
one or both of the eyes hurt;
the eyes get red and stay that way;
feel pressure in your eye;
see spots or floaters;
straight lines do not look straight;
can't see things at the side as one used to;

Maculopathy

Macular involvement in diabetic retinopathy is an emergency, and unless diagnosed in the very early stages and managed adequately, it can lead to significant visual loss (central vision loss).
It is recommended that all patients use an Amslers Recording Chart which allows early detection of maculopathy.

Look at the square (grid).
Wear your reading glasses (if you use one) and cover one eye.
Focus on the center dot for one full minute.
While looking directly at the center, be sure that all the lines are straight and clear, and all the small squares are the same size.
Repeat the test in the other eye.
If any lines or squares appear distorted, wavy, blurred, discolored, or otherwise abnormal, call your eye doctor right away.
In healthy eyes the lines are straight.

MANAGEMENT strategies for Diabetic Retinopathy

Lifestyle	30-60 minutes exercise a day, moderate alcohol consumption only, avoid obesity if possible, balanced diet including 5 portions of vegetables or fruit a day, with the minimal of animal or 'hard' vegetable fats, and very low salt.
blood pressure	130/80 or less125/75 or less if protein in urine present
HbA1c	6.5% or less with very few or preferably no hypos. If hypos develop, see expert advice. ACE inhibitors or AT11 unless young/pregnant/very low blood pressure/poorly tolerated
cholesterol	<4.66mmol/l, and statins recommended for most adult patients
Smoking	smoking 20 a day triples retinopathy (passive smoking: room-mates inhale at least 25%)

Treatment

Laser therapy
- Pan-retinal photocoagulation for proliferative retinopathy
- Focal or grid photocoagulation for macular oedema.
Medical therapy
- Corticosteroids – Triamcinolon
- Anti VEGF agents – Ranibizumab , Bevacizumab, Pegaptanib

References

Diabetes India - Site Consensus diabetes [Internet]. Diabetesindia.com. 2016 [cited 20 October 2016]. Available from: http://www.diabetesindia.com/diabetes/cons_diabetic_retinopathy.html

Diabetic neuropathy

Diabetic neuropathy is a common complication of type 1 and type 2 diabetes due to uncontrolled high blood sugar levels that result in damage to the nerves.
In cases of severe or prolonged neuropathy, patients may suffer injuries or infections in their extremities or soft tissue damage that requires amputation.
There are four main types of neuropathy:
- The most common form is peripheral neuropathy, or damage to the nerves that reach out from the brain and spine to all the parts of the body. The nerve endings in your legs and arms are the most commonly affected. Peripheral neuropathy can cause numbness, tingling, and pain in your extremities.
- The second most common type of neuropathy in people with diabetes is autonomic neuropathy. can cause problems with your digestive and urinary tracts, as well as with your eyes and sex organs. A common complaint of men with diabetic neuropathy is impotence or erectile dysfunction. Cardiovascular autonomic neuropathy, which affects the heart, is a leading risk factor for death.
- A less common form of neuropathy is proximal neuropathy, also known as diabetic amyotrophy. This form of neuropathy is more commonly seen in older people with type 2 diabetes. It most commonly affects the hips, thighs, and legs. Diabetic amyotrophy usually affects only one side of the body.
- The final type of neuropathy is focal neuropathy, or mononeuropathy, which occurs when there is damage to one specific nerve or group of nerves, causing weakness in the affected area. The pain of mononeuropathy can be extreme, but it tends to resolve itself over time and usually does not lead to long-term complications.

References

Diabetes India - Site Consensus diabetes [Internet]. Diabetesindia.com. 2016 [cited 20 October 2016]. Available from: http://www.diabetesindia.com/diabetes/cons_neuropathy.html

Diagnosis

Careful History : Questions related to the sensory (tingling, numbness, anaesthesia, parasthesias, inco-ordination), motor (wasting, weakness, nocturnal muscle cramps) and autonomic (gastrointestinal and bladder symptoms, sexual dysfunction, postural light-headedness) nervous systems, etc.
Tests for Peripheral Sensation : Check for touch, pain (pinprick) and vibration thresholds (calibrated tuning fork).
Although tests like nerve conduction studies and EMG can be done, in clinical terms, the most simple test known as the Monofilament test. This allows a very simple but clinically important study of the sensation in the feet which, if often and correctly done can help in avoiding the most dreaded of complications such as foot injuries and infections.
Motor Involvement : Check for muscle weakness and wasting.
Reflexes
Detecting Autonomic Neuropathy

Simple clinical tests for Detecting autonomic neuropathy
Tests for autonomic neuropathy		Normal response	Abnormal response
Resting heart rate			>100/minute
Heart rate response to standing	Measure R-R interval at beats 15 and 30 after the patient stands	A 30:15 ratio of less than 1.03 is abnormal
Systolic blood pressure changes on standing	Measure systolic blood pressure lying down then standing.	Decrease < 10 mm Hg	Decrease > 30 mm Hg
Heart rate response to deep breathing	Measure heart rate response to deep breathing	Increase rate > 15 beats /min	Increase < 10 beats /min

Risk factor for diabetic neuropathy

Smoking.
Age over 40 years.
History of periods of poor glycaemic control.
Prevalence increases with increased duration of diabetes.
People with signs of neuropathy are likely also to have evidence of diabetic nephropathy and diabetic retinopathy.
Hypertension.
Ischaemic heart disease.

Symptoms:

sensitivity to touch
loss of sense of touch
difficulty with coordination when walking
numbness or pain in your extremities
muscle weakness or wasting
nausea and indigestion
diarrhea or constipation
dizziness upon standing
excessive sweating
vaginal dryness in women and erectile dysfunction in men
foot ulcers
skin infections

Management:

Regular surveillance for signs of neuropathy to allow early intervention.
Tight glycaemic control.
Prevention of foot trauma.
Simple analgesia taken in advance of diurnal symptoms.
Contact dressings
Smoking avoidance or cessation.
Meditation
Acupuncture
Aldose reductase inhibitors, a-Lipoic acid
Injections of B1, B6, and B12

Diabetic nephropathy

Diabetic nephropathy is the leading cause of end-stage renal disease, accounting for 40% of new cases.
The term diabetic nephropathy is used to describe the combination of lesions that often occur concurrently in the diabetic kidney. The most common kidney lesions in people with diabetes are those that affect the glomeruli.
Various glomerular changes may occur, including capillary basement membrane thickening, diffuse glomerular sclerosis, and nodular glomerulosclerosis.

Risk factor for diabetic neuropathy

Genetic and familial predisposition
Elevated blood pressure
Poor glycemic control
Smoking
Hyperlipidemia
Microalbuminuria

The exact cause of diabetic nephropathy is unknown, but various postulated mechanisms are:

Hyperglycemia (causing hyperfiltration and renal injury)
Advanced glycosylation products
Activation of cytokines

Treatment

Adults with persistent albuminuria (>2.0 mg/mmol in men, 2.8 mg/mmol in women) should be started on an ACE regardless of blood pressure.
Intensive treatment of blood pressure to achieve target <130/80 mmHg
Reduce salt in diet
Reduce alcohol consumption.

References

Diabetes India - Site Consensus diabetes [Internet]. Diabetesindia.com. 2016 [cited 20 October 2016]. Available from: http://www.diabetesindia.com/diabetes/cons_kidney_disease.html

Diabetic Ketoacidosis

A serious diabetes complication where the body produces excess blood acids (ketones). Usually results from omitting insulin in type 1 DM or increase insulin requirements in other illness (e.g. infection, trauma) in type 1 DM and type 2 DM.
Due to break down of fat and muscle

Signs and symptoms

Fatigue, muscle cramps, flushed facial appearance,
Weight loss, nausea, vomiting, abdominal pain
dehydration, acid smelling breath
rapid deep breathing,
Shock fruity breath odor,
Altered consiousness
hypotension and tachycardia
Coma

Diagnosis

Immediate diagnosis
- capillary glucose, urinary glucose and ketones
Urgent for assessment and treatment
- Blood glucose,
- Blood gases,
- Electrolytes, urea, creatinine
- WBC
- consider cardiac monitor, blood culture, urine culture and chest x-ray

Diabetic Keto Acidosis (DKA) Laboratory findings

Blood Glucose	>13.8 mmol/L (250mg/dL)
Ketones	Urine: moderate to large Blood: >3mmol/L
Osmolality	Increased – high blood glucose and urea/creatinine, dehydration
Electrolytes	Low/normal Na+ and Cl- Low/normal/high K+= (often misleading) Low HCO3 (normal 23-31)
Anion Gap	≥ 10 mild > 12 moderate to severe
Blood Gases	pH ≤ 7.3, HCO3 ≤ 15 (mild) pH < 7.0, HCO3 < 10 (severe)

DKA management

Management:
- Fluid administration: Rapid fluid administration to restore the vascular volume,
- IV infusion of insulin to restore the metabolic abnormalities. Titrate the dose according to the blood glucose level.
- Potassium and phosphate can be added to the fluid if needed.
Follow up:
- Metabolic improvement is manifested by an increase in serum bicarbonate or pH.

References

Kitabchi AE, Guillermo E, Umpierrez GE, Fisher JN. (2009).
Management of hyperglycemic crises in patients with diabetes. Diabetes Care, 32, 1335-1343. Canadian Diabetes Association 2008.

Macrovascular diseases

Diabetes mellitus is a major risk factor for coronary artery disease, cerebrovascular disease, and peripheral vascular disease.
Multiple risk factors for vascular disease, including obesity, hypertension, hyperglycemia, hyperlipidemia, altered platelet function, and elevated fibrinogen levels, frequently are found in people with diabetes.
Cardiovascular disease affects the heart and blood vessels and may cause fatal complications such as coronary artery disease (leading to heart attack) and stroke. Cardiovascular disease is the most common cause of death in people with diabetes. High blood pressure, high cholesterol, high blood glucose and other risk factors contribute to increasing the risk of cardiovascular complications.

Risk factors includes:

Cigarette smoking
Diabetes mellitus (fasting plasma glucose equal to or greater than 126 mg/dL
Hypertension (Blood Pressure equal to or greater than 140/90 mmHg)
High LDL cholesterol (equal to or greater than 100)
Low HDL cholesterol (men less than 40 mg/do, women less than 50)
Obesity (Body Mass Index greater than 25)
Lack of physical activity
Family history of premature heart disease (presence of heart disease in male first-degree relative less than 55 years & in female first degree relative less than 65 years).
Age (men greater than 45 years; women greater than 55 years)

Type 2 diabetes	LDL-C < 2.5 mmol/L (< 95 mg/dL) TG < 2.3 mmol/L (<200 mg/dL) HDL-C > 1.0 mmol/L (> 39 mg/dL)
Most adults with diabetes	LDL-C < 2.6 mmol/L (< 100 mg/dL) TG < 1.7 mmol/L (<150 mg/dL) HDL-C > 1.0 mmol/L (> 40 mg/dL) for men HDL-C > 1.3 mmol/L (> 50 mg/dL) for women

Lipid treatment:

Use HMG-CoA reductase inhibitors (statins)
Increase physical activity
Attain and maintain a healthy weight
Reduce total and saturated fat
Increase monosaturated fat and flavonoids

Treatment of heart failure:

ACE inhibitors
Beta blockers
Diuretics
Fluid management

References

International Diabetes Federation. (2005). Global Guidelines for Type 2 Diabetes. Brussels: International Diabetes Federation.
American Diabetes Association. (2010) Clinical Practice Recommendations. Diabetes Care, 33(suppl 1).

Hypoglycemia

Hypoglycaemia, which literally means “low blood glucose” can arise from many causes, and can occur at any age.
Blood glucose level of 4 mmol/L (~72 mg/dl) or below is considered hypoglycaemia.
There are many possible causes for hypoglycaemia. The obvious risks include:
- Consuming too little carbohydrate
- Missing a meal or eating a meal later than the usual time
- Taking excessive doses of insulin or blood glucose-lowering medicines
- Fasting or mal nourishment
- pregnancy
- Liver diseases or kidney failure
- endocrine diseases
- Other medication or drugs including alcohol
- Physical activity may also provoke low levels of glucose at the time of the activity.
People should monitor blood glucose frequently after exercise and learn how to adjust their food intake and insulin doses accordingly.

Symptoms of hypoglycaemia

Mild	Moderate	Severe
Capable of self treatment	May require prompting	Not capable of self-treatment
Tremors, palpitation, sweating, hunger, fatigue	Headache, mood changes low attentiveness	Conscious or unconscious
Autonomic	Neuroglycopenic	Neuroglycopenic

Treatment

Mild or Moderate
- Test if possible
- 15 g glucose, retest
  - Glucose tablets or gel
  - ½ cup fruit juice
  - 3 tea spoons sugar or honey
- Retreat if level remains low
Severe
- 20 g glucose
- Glucagon
- Intravenous dextrose
- Manage seizure – place person on their side if not too agitated.

Managing diabetes during disaster

Disaster is an exceptional event which suddenly kill or injure number of people or an unforeseen event that individuals have little control over.
During disaster individuals should cope up the situation by
- Knowing the type of disaster most likely to occur in your area.
- Prevention - Preplanning
- In an emergency putting a plan into action
- Immediately after the emergency - coping until help arrives.
An individual should have his Diabetes disaster kit which includes:
- Diabetes disaster kit – Important documents
  - Emergency contact information
  - Medical providers name, address, phone no.
  - Health insurance information
  - Prescriptions
  - Medical history
  - Medication list including non-prescription medications and allergies
  - Have both brand and generic name of medicine on list.
- Diabetes disaster kit – medications
  - Insulin
  - Diabetes pills
  - Other prescription medications
  - Over the counter medications
  - Medications for nausea/vomiting or diarrhoea
  - Ideally should have enough medicines to last for a considerable amount of time.
  - It is very important that medicines in emergency kits are checked on a regular basis.
  - Check expiration dates an replace if necessary.
  - Keep repeat prescriptions in your kit.
- Diabetes disaster kit – medication storage
  - Insulin may be stored at room temperature for 28 days (15 – 30oC)
  - Insulin pens can be stored at room temperature according to manufactures instructions.
  - Excessive cold, heat or light can adversely affect insulin.
  - There is an insulin “cooler” on the market but it does require to activate.
- Diabetes disaster kit – medication tips
  - If using cloudy insulin, make sure its mixed well before using
  - If using clear insulin make sure it is not cloudy and does not have anything floating in it.
  - If insulin contains particles, sticks to the side of the bottle, or is clumpy, it should not be used
  - In an emergency it may be necessary to reuse syringes or lancets but do not share needles or lancets with others.
References
- International diabetes federation. Education module, 2011.

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