diabetes should be prevented , diagnosed and treated in the early stage .

1. MEDICINE UPDATE
FOR ALL DOCTORS
DIABETES MELLITUS
Indoredrishti.wordpress.com

2. DR DINESH MITTAL DR SONALEE MITTAL
DRISHTI EYE HOSP VIJAYNAGAR INDORE

3. •Diabetes is a disease with increasing
global incidence, affecting more than
371 million people and causing 4.8
million deaths in 2012
•India has the world’s second largest
population of people with diabetes,
affecting about 63 million people with
about a half of them still undiagnosed

4. DIABETES
• The prevalence of diabetes mellitus in the
United States is estimated to be as high
as 8%. Obesity is a major contributing
factor and continues to increase in
prevalence yearly
• Moderate exercise and weight loss can
prevent the onset of type 2 diabetes
mellitus in patients at risk for
development of the disease .

6. •The risk of hyperglycemia is 2 times as
great in individuals who are 20% above
ideal body weight, compared with those at
ideal body weight; the risk is 4 times, 8
times, 16 times, and 32 times as great in
those 40%, 60%, 80%, and 100% above
ideal body weight, respectively.

7. Basics of Glucose Metabolism
• The plasma glucose level is reduced by a single
hormone, insulin. In contrast, 6 hormones increase the
plasma glucose level: somatotropin, adrenocorticotropin,
cortisol, epinephrine, glucagon, and thyroxine. All of
these hormones are secreted as needed to maintain
normal serum glucose levels in the face of extremely
variable degrees of glucose intake and utilization. In the
fed state, anabolism is initiated by increased secretion
of insulin and growth hormone. This leads to conversion
of glucose to glycogen for storage in the liver and
muscles, synthesis of protein from amino acids, and
combination of fatty acid and glucose in adipose tissue
to form triglycerides.

8. Basics of Glucose Metabolism
• In the fasting state, catabolism results from the
increased secretion of hormones that are antagonistic to
insulin. In this setting, glycogen is reduced to glucose in
the liver and muscles, proteins are broken down into
amino acids in muscles and other tissues and transported
to the liver for conversion to glucose or ketoacids, and
triglycerides are degraded into fatty acids and glycerol in
adipose tissue for transport to the liver for conversion to
ketoacids and glucose (or for transport to muscle for use
as an energy source).

10. Basics of Glucose Metabolism
• A lean adult without diabetes secretes approximately 33
units of insulin per day. If pancreatic β- cell mass is
reduced (as in type 1 diabetes), then catabolic
hormones results in fasting hyperglycemia, and
persistent catabolism may lead to fatal diabetic
ketoacidosis if insulin therapy is not started. Thus,
insulin-dependent diabetic patients require a continuous
baseline dose of insulin, even in the fasting state: some
level of insulin is needed to offset the effect of all the
other hormones .

11. Basics of Glucose Metabolism
• In an obese adult, insulin secretion can increase almost
fourfold, to 120 units per day. In this state, the plasma
glucose level may rise only slightly, but pancreatic β-cell
mass increases. When serum insulin levels are elevated,
number of insulin receptors on surface of insulin-
responsive cells actually decreases, and formerly insulin-
sensitive tissues become resistant to the glucose-
lowering effects of both endogenous and exogenous
insulin. This condition may progress to fasting
hyperglycemia and type 2 diabetes .

12. Prediabetic disorders
• Impaired glucose tolerance (IGT) is the diagnosis when a
standard 75-g OGTT yields a 2-hour plasma glucose level of
≥140 mg/dL to <200 mg/dL. A separate category, impaired
fasting glucose (IFG), requires a fasting plasma glucose level of
≥110 mg/dL to <126 mg/dL. Both conditions can be considered
early stages of type 2 diabetes and are often called prediabetic
states. For instance, type 2 diabetes develops in 30%–50% of
patients with IGT within 10 years of diagnosis. Although there
is a great deal of overlap, IGT and IFG are not identical states.
An HbA1c value of at least 6.0% but below 6.5% also denotes
prediabetes.
• Patients with these conditions have an elevated risk of
macrovascular disease compared with persons with normal
glucose tolerance. Accumulating evidence also suggests an
increased risk of microvascular disease, including nephropathy
and retinopathy.

13. Metabolic syndrome
• Closely associated with type 2 diabetes, metabolic
syndrome is not a disease but a collection of disorders.
The clinical syndrome includes obesity, lipid
abnormalities, hypertension, and some type of glucose
intolerance , risk factors common to both diabetes and
cardiovascular disease. Men with a majority of
metabolic syndrome features have roughly 4 times the
risk of coronary heart disease and 25 times the risk of
diabetes as those without these abnormalities.
Metabolic syndrome represents a profound public
health risk, and treatment of the syndrome may have a
significant impact on preventing diabetes and
cardiovascular diseases.

14. Clinical Presentation of Diabetes
• The classic symptoms of diabetes mellitus are
polyuria, polydipsia, and polyphagia. Type 1 diabetes
tends to present more acutely than type 2, and the
diagnosis is usually made based on the presence of
these classic symptoms in association with an elevated
plasma glucose level. The diagnosis of type 2 diabetes
often depends more on laboratory testing, as patients
may have abnormal glucose metabolism long before
overt symptoms develop. Other important historical
findings that suggest the diagnosis of diabetes include
complications during pregnancy or birth of large
babies, reactive hypoglycemia, family history,
advanced vascular disease, impotence, leg
claudication, and neuropathy symptoms.

15. Clinical Presentation of Diabetes
• Physical findings, particularly in type 2 diabetes,
may include obesity, hypertension, arteriopathy,
neuropathy, genitourinary tract abnormalities
(especially recurrent Candida infections or
bacterial bladder or kidney infections), periodontal
disease, foot abnormalities, skin abnormalities,
and unusual susceptibility to infections.

16. Definition, Diagnosis
• The ADA recommends a diagnosis of diabetes mellitus
• when 1 of the following 4 criteria are met and
confirmed with retesting on a subsequent day:
• HbA1c ≥6.5% (<5.7% = normal)
• FPG level ≥126 mg/dL (7.0 mmol/L)
• 2-hour plasma glucose level ≥200 mg/dL (11.1 mmol/L)
with 75-g OGTT
• random plasma glucose level ≥200 mg/dL (11.1 mmol/L)
in a patient with classic symptoms of hyperglycemia,
including polyphagia, polyuria, and polydipsia

17. The importance of glucose
control

21. OVERALL GOALS
• The goals of therapy for type 1 or type 2 diabetes
mellitus (DM) are to
• ( 1 ) eliminate symptoms related to hyperglycemia，
• (2) reduce or eliminate the long-term microvascular and
macrovascular complications of DM and
• (3) allow the patient to achieve as normal a lifestyle as
possible.
• Symptoms of diabetes usually resolve when the plasma
glucose is < 1 1 . 1 mmol/L (200 mg/dL) ， and thus
most DM treatment focuses on achieving second and
third goals.

24. Type 1 diabetes
•Type 1 diabetes was previously called
insulin-dependent diabetes mellitus or
juvenile-onset diabetes. Although incidence
peaks around the time of puberty,
approximately 25% of cases present after
35 years of age. This form of diabetes is
due to a deficiency in endogenous insulin
secretion secondary to destruction of
insulin-producing β-cells in the pancreas.

25. Type 2 diabetes
• Type 2 diabetes was formerly known as non–insulin-
dependent or adult-onset diabetes mellitus. Patients with
type 2 diabetes are usually, but not always, older than 40
years at presentation. Obesity is a frequent finding and,
in the United States, is present in 80%–90% of these
patients. Other risk factors for type 2 diabetes include
hypertension, a history of gestational diabetes, physical
inactivity, and low socioeconomic status. This form of
diabetes mellitus is frequently undiagnosed for years
because hyperglycemia develops slowly and patients are
often asymptomatic. Despite minimal symptoms, these
patients are at increased risk for microvascular and
macrovascular complications.

31. CHOICE OF INITIAL GLUCOSE-
LOWERING AGENT
• The level of hyperglycemia and the patient's
individualized goal should influence the initial choice of
therapy.
• Assuming that maximal benefit of MNT and increased
physical activity has been realized， patients with mild
to moderate hyperglycemia (FPG < 200-250 mg/dL ) often
respond well to a single， oral glucose-lowering agent.
Patients with more severe hyperglycemia (FPG > 250
mg/dL ) may respond partially but are unlikely to achieve
normoglycemia with oral monotherapy.
• A stepwise approach that starts with a single agent and
adds a second agent to achieve the glycemic target can
be used.

32. Risk Factors for Type 2 Diabetes
Mellitus

33. Prevention of Diabetes Mellitus
• the risk of progression from IGT to type 2 diabetes
can be markedly reduced (by approximately 50%
over several years) with lifestyle modifications
such as a combination of diet and exercise therapy.
The amount of weight loss and exercise required to
achieve this result is surprisingly modest. For
instance, in the Diabetes Prevention Program,
patients who were asked to perform only 150
minutes of brisk walking a week (a little over 20
minutes a day) lost only about 12 pounds of weight
on average but reduced their risk of diabetes
development by 50%.

34. Treatment Goals for Adults with
Diabetesa

37. Pharmacologic Comparisons
between Oral Hypoglycemic Drug
Classes

38. Pharmacologic Comparisons
between Oral Hypoglycemic Drug
Classes

40. First line
• The majority of patients and certainly
those who are overweight should start
METFORMIN first line. This should be
started at 500 mg once or twice a day
and the dose increased after 5–7 days .
Increasing the dose gradually may offset
the gastrointestinal side effects that
many patients fail to tolerate .

41. Metformin
• Metformin has a number of beneficial actions in
diabetes. It reduces hepatic gluconeogenesis,
increases insulin sensitivity and reduces carbohydrate
absorption from the gastrointestinal tract. It also
improves circulating free fatty acids and VLDL levels.
The UKPDS study suggested that metformin improves
cardiovascular risk independently of its effect on blood
glucose levels. Very occasionally, metformin causes
reduction in vitamin B12 absorption, and serum B12
levels should be checked in patients taking metformin
who develop peripheral neuropathy.

42. First line
• Non-obese patients may be insulin-deficient
(particularly if they have actually lost weight) and
could start a sulphonylurea first rather than
metformin, but metformin has other benefits and so
could be co-prescribed from the start in this situation.
The sulphonylurea is titrated upwards according to
fasting blood glucose levels if available, or HbA1c .

43. Second line
• If the HbA1c is still not in target after 2–3 months, offer
a second agent. This could either be a sulphonylurea, a
glitazone, or a gliptin . Glitazones should be avoided in
those with, or at risk of heart failure. If the patient is
unwell or actually losing weight then insulin should be
started without delay. This may also be appropriate if
the HbA1c is still very high (e.g. over 9% ).

44. Third line
• ‘Triple therapy’ using metformin, a sulphonylurea and
either a glitazone or sitagliptin is licensed, but many
patients using this combination are candidates for
insulin, and this should always be considered before
starting a third oral drug. Patients starting insulin can
continue their oral medication, but an intensive
insulin therapy regimen may be simpler if
sulphonylurea is withdrawn, as the insulin is providing
a similar effect exogenously.

45. INSULIN
• insulin treatment for T2DM is usually started when the
initial oral therapy, in double or triple combination and
at the maximum tolerated doses fails to achieve optimal
glycaemic control. recent guidelines recommend
initiation of insulin early in the course of disease,
especially in patients with HbA1c > 9% as it is unlikely
to achieve glycaemic targets with the use of oral agents
alone .

51. Starting insulin in general
practice
• Insulin can be started in most type 2 patients in general
practice. the usual preferred regimen is a twice daily
dose of premixed insulin such as Novomix 30 or Mixtard
30 given before breakfast and before the evening meal. It
is usual to start at 6–8 u twice a day with home blood
glucose monitoring. The monitoring technique should be
taught prior to commencing (and not at the same time
as) the insulin.

52. insulin
• The insulin dose can be titrated upwards according to
blood glucose levels, usually in increments of 2–4
units,. An alternative is to start with a long-acting
analogue such as glargine or detemir at 8 units in the
evening, titrating upwards according to fasting
glucose levels. Conversion to a more flexible regimen
can be achieved later on, either through the addition
of short- or rapid-acting insulins with meals to create
a basal-bolus regimen, or by changing over to a
premixed insulin twice or three times a day

56. •long-acting insulins (NPH， glargine，
or detemir) supply basal insulin，
whereas regular， insulin aspart，
glulisine，or lispro insulin provides
prandial insulin. Short-acting insulin
analogues should be Injected just
before (< 10 min) or just after a meal;
regular insulin is given 30-45 min
prior to a meal.

58. Multiple-component insulin regimen

59. • . A multiple-component insulin regimen
consisting of long-acting insulinA
glargine or detemir may be required
each day to provide basal insulin
coverage and three shots of glulisine,
lispro, or insulin aspart to provide
glycemic coverage for each meal.

61. •. B. The injection of two shots of
long-acting insulin (NPH) and short-
acting insulin [glulisine, lispro,
insulin aspart (solid red line), or
regular (green dashed line)]. Only
one formulation of short-acting
insulin is used.

63. • C. Insulin administration by insulin infusion device is
shown with the basal insulin and a
bolus injection at each meal. The
basal insulin rate is decreased during
the evening and increased slightly
prior to the patient awakening in the
morning. Glulisine, lispro, or insulin
aspart is used in the insulin pump.

64. • In general， individuals with type 1 DM require 0 . 5 - 1
U/kg per day of insulin divided into multiple doses， with -
50% of the insulin given as basal insulin. one commonly
used regimen consisted of twice-daily Injections of NPH
mixed with a short-acting insulin before the morning and
evening meals (Fig. 4 1 8 - 1B). Such regimens usually
prescribe two-thirds of the total daily insulin dose in the
morning (with about two-thirds given as long-acting
insulin and one-third as short-acting) and one-third before
the evening meal (with approximately one half given as
long-acting insulin and one-half as short-acting) .

70. Insulin Therapy
• OVERVIEW
• • Patients presenting with type 1 diabetes require
insulin without delay to avoid ketoacidosis
• • An increasing proportion of type 2 patients will
require insulin to achieve modern glycaemic
control targets
• • The majority of type 2 patients requiring insulin
can have this treatment initiated in primary care

71. 1. Introduction
• Insulin replacement therapy is essential for a patient
with type 1 diabetes and is needed to achieve good
glycaemic control in many patients with type 2 diabetes
once other agents are no longer able to achieve this
effectively. For patients with previously poor glycaemic
control insulin has dramatic effects and can enhance
wellbeing in a way that other therapies cannot match.
Despite these obvious benefits, many patients who have
previously taken tablets resist going onto insulin therapy,
principally because it is an injectable preparation.
• Insulin therapy also requires much more active
involvement by the patient to adjust the doses.

73. Insulin regimens Starting insulin in
type 1 diabetes
• Many type 1 patients can start treatment with a twice-
daily biphasic regimen, usually about 8 units twice a
day and then the dose is optimised. However, in
younger patients in particular, a more flexible method is
the basal-bolus regime where a long-acting insulin is
given at bedtime and meals are covered by soluble
insulin or a very short-acting analogue.

75. Basal-bolus regime
• an intermediate- or long-acting acting insulin is used at
bedtime and meals are covered using a short-acting
insulin or a rapid-acting insulin analogue. A long-acting
insulin analogue such as insulin glargine or insulin detemir
is often used in the UK now as the basal insulin. The
timing of the rapid-acting insulin can vary according to the
timing of meals. This is convenient for those at work or at
college.

76. Twice or three times a day
biphasic regimen
• Some patients opt to have twice-daily biphasic
mixtures taken at breakfast and with an evening
meal. This can be increased by adding in a lunch
time dose if using a biphasic with a rapid acting
component, but there may in some cases be a risk
of overlap between the lunchtime and evening
doses. Occasionally such patients may require a
short-acting or rapid-acting insulin with lunch
instead of the biphasic.

77. Starting insulin in type 2
diabetes
• For some type 2 patients where symptom control is main
aim of therapy, it may be appropriate to provide once-
daily insulin injection with a long-acting insulin analogue.
For most patients, however, pre-mixed insulin or insulin
analogue is preferred. Many patients with type 2 diabetes
also elect to go on a basal bolus regimen, which involves
four or more injections a day because of the flexibility it
offers. For most patients with type 2 diabetes, however, a
twice or three times a day regimen of pre-mixed
analogues is useful. Maintaining glycaemic control in a
patient with type 2 diabetes represents more of a
challenge as their needs will change along with disease
progression

78. Starting insulin in type 2
diabetes
• The doses are increased usually in increments of 2
or 4 units with each dose until glucose control is
satisfactory, taking care to avoid hypoglycaemia.
• This is important to explain to the patient and also
to alter insulin doses and the regime as
requirements increase. Patients should also be
warned about weight gain, particularly in those
with type 2 diabetes and concomitant attention to
control of obesity is valuable in mitigating this.

80. Final recommendations
• 1. EXERCISE
• 2 . WEIGHT REDUCTION
• 3 . METFORMIN
• 4. SULFONYL UREA
• 5. POIGLITAZONE
• 6. ADD MIXTARD INSULIN PEN . START BEDTIME
DOSE OF 8 UNITS AND INCREASE ACCORDING TO
BLOOD GLUCOSE MONITORING .

81. THANK
YOU
DR DINESH
DR SONALEE