DIABETES, OBESITY AND METABOLIC SYNDROME

MEDICINE B - ENDOCRINOLOGY
DR. BERMUDEZ

DIABETES MELLITUS (DM) • The values of the following are not applied for the diagnosis of

1
gestational DM:
• According to International Diabetes Federation o Fasting plasma glucose (FPG)
o In 2017, proximately 425 million adults were living with o 2h plasma glucose (PG) after a glucose challenge
diabetes and by 2045, this is expected to rise to 629 million o Hemoglobin A1c (HbA1c)
o The proportion of people with type 2 DM is increasing in
most countries and 79% of them are living in low and
middle-income countries
o The greatest number of people with DM are between 40
and 50 years of age
o 1 in 2 people with diabetes were undiagnosed
o Diabetes caused 4 million deaths
o The Western Pacific Region has the highest number of
cases in which PH belongs

• Diabesity Epidemic in the Philippines

o There are more patients who are pre-diabetic à more
patients will develop type 2 DM in the next few years
o In the national survey estimating the prevalence of
diabetes and pre-diabetes (using the criteria of WHO), in 17
regions in our country:
§ 7.2%: national prevalence of diabetes
§ 10.2%: national prevalence of pre-diabetes

REMEMBER ALL THE VALUES FOR NORMAL, PRE-DIABETES AND DIABETES

CLASSIFICATIONS OF DM
• DM refers to a group of metabolic disorders that share the CRITERIA FOR THE DIAGNOSIS OF DM
phenotype of hyperglycemia and there are several classifications • The diagnosis of DM is based on the following criteria

1. Type 1 Diabetes Fasting Plasma Glucose ≥7.0 mmol/L (126 mg/dL)

o Due to autoimmune beta-cell destruction, usually leading to
absolute insulin deficiency
2. Type 2 Diabetes
o Due to a progressive loss of b-cell insulin secretion
frequently on the background of insulin resistance)
3. Gestational Diabetes (GDM)
o Diabetes diagnosed in the 2nd or 3rd trimester of
pregnancy that was not clearly overt diabetes prior to
gestation
4. Specific Types of Diabetes due to Other Causes
o Monogenic diabetes syndromes
§ neonatal diabetes
§ maturity-onset diabetes of the young (MODY)
o Diseases of the exocrine pancreas
§ cystic fibrosis
§ pancreatitis)
o Drug- or chemical-induced diabetes
§ glucocorticoid use, in the treatment of HIV/AIDS
§ after organ transplantation
SPECTRUM OF GLUCOSE HOMEOSTASIS AND DM
REFER TO THE TABLE AT THE RIGHT SIDE WITH STAR
• The spectrum from normal glucose tolerance to diabetes in type
1 DM, type 2 DM, specific types of diabetes, and gestational DM is
shown from left to right
• In most types of DM, the individual traverses from normal glucose
tolerance to impaired glucose tolerance to overt diabetes
• Arrows indicate that changes in glucose tolerance may be
bidirectional in some types of diabetes.
• For example:
o Individuals with type 2 DM may return to the impaired
glucose tolerance category with weight loss
o In gestational DM, diabetes may revert to impaired glucose
tolerance or even normal glucose tolerance after delivery.
OR
Hemoglobin A1c ≥ 6.5%
OR
2-h Plasma Glucose ≥200 mg/dL (11.1 mmol/L) during OGTT
OR
Signs and symptoms of DM PLUS RBS ≥11.1 mmol/L (200
mg/dL)
• Remember: Hemoglobin A1c should only be used if this is
standardized by the National Glycohemoglobin Standardization
Program (NGSP)
• In PH, most of Hemoglobin A1c assay are not standardized by
NGSP
o We only use Hemoglobin A1c as a parameter to monitor
treatment response and not as a parameter for diagnosing
DM
Criteria for Testing for Diabetes or Pre-diabetes in
Asymptomatic Adults
1. Testing should be considered in overweight or obese (BMI ≥ 25 kg/m2
or ≥ 23 kg /m2 in Asian Americans) adults who have one or more of the
ff risk factors:
• First-degree relative with diabetes
• High-risk race/ethnicity (e.g. African American, Latino, Native
American, Asian American, Pacific Islander)
• History of CVD
• Hypertension (≥ 140/90 mmHg or on therapy for HTN)
• HDL cholesterol level < 35 mg/dL (0.90 mmol/l) and/or a
triglyceride level >250 mg/dL (2.82 mmol/L)
• Women with PCOS
• Physical inactivity
• Other clinical conditions associated with insulin resistance (e.g.
severe obesity, acanthosis nigricans)
2. Patients with pre-diabetes (A1c ≥ 5.7% [39 mmol/mol], IGT or IFG)
should be tested yearly
3. Women who were diagnosed with GDM should have lifelong testing at
least every 3 years

Reference: PPT + Recording (2021) + Harrison’s 20th ed. Page 1 of 11

 4. For all other patients, testing should begin at age 45 years INSULIN SECRETION
5. If results are normal, testing should be repeated at a minimum of 3-
year intervals, with consideration of more frequent testing depending
on initial results and risk status

• Widespread screening for diabetes is recommended

• The American Diabetes Association recommends:
o Screening of all individuals age 45 yrs old and above every
3 years
o Screening of individuals at an earlier age if they are
overweight and have one additional risk factor for diabetes
such as the ones listed above in the table (#1)
o Patients with pre-diabetes should be tested yearly
o Women who are diagnosed with GDM have lifelong testing
at least every 3 years
o If results are normal, testing should be repeated at a
minimum of 3-year intervals, with consideration of more
frequent testing depending on initial results and risk status

INSULIN STRUCTURE AND SYNTHESIS

• How insulin is secreted from the pancreatic beta-cells is mediated

by several factors
o Glucose and other nutrients regulate insulin secretion
• Glucose: key regulator of insulin secretion
o Glucose levels >3.9 mmol/L (70 mg/dL) stimulate insulin
synthesis, primarily by enhancing protein translation and
processing.
o Glucose is transported by a glucose transporter
§ Glucose Transporter 1 and 2 in humans
o Subsequent glucose metabolism by the beta-cell alters ion
channel activity leading to insulin secretion
• The SUR receptor is the binding site of some drug that act as
insulin secretagogue

TYPE 1 DIABETES MELLITUS

• Insulin • Type 1 DM is the result of interactions of genetic, environmental,

o It is produced by the beta cells of the pancreatic islets and immunologic factors that ultimately lead to immune-
o It is initially synthesized as a single-chain 86-amino-acid mediated destruction of the pancreatic beta cells and insulin
precursor polypeptide, preproinsulin deficiency
• Preproinsulin (Precursor of Insulin) • Type 1 DM can develop at any age, but most commonly develops
o It undergoes subsequent proteolytic processing that before 20 years of age.
removes the amino-terminal signal peptide, giving rise to
proinsulin
• Proinsulin
o structurally related to insulin-like growth factors I and II,
which bind weakly to the insulin receptor.
o Cleavage of an internal 31-residue fragment from proinsulin
generates C-peptide with the A (21 amino acids) and B (30
amino acids) chains of Insulin being connected by disulfide
bonds.
• C-peptide and Mature Insulin
o Stored together and co-secreted from secretory granules
in the beta cells
o C-peptide: cleared more slowly than insulin
§ it is a useful marker of insulin secretion and allows
discrimination of endogenous and exogenous
sources of insulin in the evaluation of hypoglycemia
SUMMARY OF INSULIN SYNTHESIS

Preproinsulin Temporal model for development of type 1 diabetes

• In susceptible individuals, the autoimmune process is thought to

be triggered by infectious or environmental stimulus
Proinsulin • In the majority of patients, autoantibodies against beta cell
antigens appear after this triggering event, followed by
progressive loss of insulin secretion.
C-peptide Insulin • Features of diabetes do not become evident until a threshold loss
of insulin secretion and beta cell mass occurs

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• 3 Stages in the Development of Islet Autoantibodies and a • Dysfunction of the beta-cells is the final common denominator in
Gradual decline in Beta cell function and Mass diabetes mellitus
• Eleven currently known mediating pathways of hyperglycemia
Stage 1 • Characterized by the development of two known as Egregious Eleven are shown in the figure above
or more islet cell autoantibodies but there • Many of these contribute to beta-cell dysfunction such as in:
is a maintenance of normoglycemia. o Liver
• Asymptomatic phase and individuals o Muscle
already have antibodies o Adipose Tissue
Stage 2 • Defined by continued autoimmunity and o Brain
the development of dysglycemia o Colon
• Pre-diabetic stage o Immune dysregulation or Inflammation
Stage 3 • Defined by the development of • Others, result from beta-cell dysfunction through downstream
hyperglycemia that exceeds the diagnostic effects such as
criteria for the diagnosis of diabetes. o Reduced insulin
• Overt diabetes stage o Decreased incretin effect
o Alpha-cell defect
PATHOPHYSIOLOGY OF TYPE 1 DM o Stomach/small intestine via reduced amylin
• Major susceptibility gene for type 1 DM is located in the HLA region o Effects in the kidneys
• NOTE: Study the figure of Egregious Eleven
on chromosome 6 (MHC II)
• Haplotypes most strongly associated with type 1 DM
o DQA1*0301 TYPE 2 DIABETES MELLITUS
o DQB1*0302 • Insulin resistance and abnormal insulin secretion are central to
o DQB1*0201 the development of type 2 DM
• Pathology: insulitis • Type 2 DM likely encompasses a range of disorders with the
o Pathologically, the pancreatic islet have modest infiltration common phenotype of hyperglycemia
of lymphocytes, a process term insulitis • Genetic Considerations
• Pancreatic islet molecules targeted by the autoimmune process o The disease is polygenic and multifactorial, because in
include: addition to genetic susceptibility, environmental factors
o Proinsulin and insulin (such as obesity, poor nutrition, and physical inactivity)
o Glutamic acid decarboxylase modulate the phenotype.
o Islet Cell Antigens or ICA-512/IA-2
o Beta cell–specific zinc transporter (ZnT-8). PATHOPHYSIOLOGY OF TYPE 2 DM
• ICAs are present in: • Type 2 DM is characterized by:
o Majority of individuals (>85%) diagnosed with new-onset o Impaired insulin secretion
type 1 DM o Insulin resistance
o In a significant minority of individuals with newly diagnosed o Excessive hepatic glucose production
type 2 DM (5–10%) o Abnormal fat metabolism
o Occasionally in individuals with GDM (<5%) o Systemic low-grade inflammation
• Putative environmental triggers
o Viruses • Insulin resistance syndromes
§ Coxsackie o Metabolic syndrome/ IR syndrome/ Syndrome X
§ Rubella o Mutations in insulin receptor
§ Enteroviruses most prominently § Type A: affects young women and is characterized
o Bovine milk proteins by severe hyperinsulinemia, obesity, and features of
o Nitrosourea compounds hyperandrogenism
o Vitamin D deficiency § Type B: affects middle-aged women and is
o Environmental toxins characterized by severe hyperinsulinemia, features
of hyperandrogenism, and autoimmune disorders
BETA-CELL-CENTRIC CONSTRUCT: EGREGIOUS ELEVEN o PCOS
o Lipodystrophies

DIABETES PREVENTION PROGRAM

• Diet and exercise delayed development of DM by 58% in patients
with Impaired Glucose Tolerance (IGT)
• Metformin delayed diabetes by 31%

Type 2 DM is preceded by impaired glucose tolerance or impaired fasting

glucose. Life style modifications and pharmacologic agents prevent or
delayed the onset of DM

Individuals with prediabetes or increased risk of diabetes should be

referred to a structured program to reduce body weight and increase
physical activity as well as being screened for cardiovascular disease.

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 MATURITY-ONSET DIABETES OF THE YOUNG (MODY) APPROACH TO THE MANAGEMENT OF HYPERGLYCEMIA

TYPE GENE AFFECTED

MODY Type 1 Hepatocyte Nuclear
Transcription Factor (HNF) 4α
MODY Type 2 Glucokinase gene
MODY Type 3 HNF-1α
MODY Type 4 Pancreatic and Duodenal
Homeobox 1
MODY Type 5 HNF-1β

• Several monogenic forms of DM have been identified

• More than 10 different variants of MODY (common ones are listed
in the table)

GOALS OF THERAPY
• The goals of therapy for type 1 or type 2 diabetes mellitus (DM)
are:
o Eliminate symptoms related to hyperglycemia
o Reduce or eliminate the long-term microvascular and
macrovascular complications of DM
• We have to balance the benefits of glycemic control with its
o Allow the patient to achieve as normal a lifestyle as
potential risks
possible.
o Taking to account the adverse effects of glucose lowering
• Although glycemic control is central to optimal diabetes therapy,
medications particularly hypoglycemia, patient’s age and
comprehensive diabetes care of both type 1 and type 2 DM should
health status among other concerns
also detect and manage DM-specific complications and modify
• For instance, an elderly with multiple co-morbid conditions, we
risk factors for DM-associated diseases.
can set a less stringent HbA1c goal

PATIENT-CENTERED GLYCEMIC MANAGEMENT IN TYPE 2 DIABETES

• Management of diabetes requires control of:

o Glycemia
o Cardiovascular risk factor management
o Regular follow-up
o Patient-centered approach to enhance patient
engagement in self-care activities (most important)

• The management plan should be taken into account the patient’s:

Age Preferences for care
Cognitive abilities Life Expectancy
School or work Cultural factors
schedules and Literacy and
conditions numeracy
Health beliefs Diabetes
Support systems complications and
Eating Patterns duration
Physical Activity Co-morbidities
Social situations Health priorities
Financial concerns Other medical
conditions
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GLUCOSE LOWERING MEDICATIONS IN TYPE 2 DM: APPROACH • Pinggang Pinoy can be used side by side by the existing dietary
• Metformin Nutritional Guide Pyramid for Filipinos but it will not replace it
o Should be started at the time type 2 DM is diagnosed unless • According to FNRI, Pinggang Pinoy is a quick and easy guide on
there are clear contraindications how much to eat per meal time while the Nutritional Guide
o For most patients, this will be monotherapy in combination Pyramid for Filipinos shows a glance of a whole day intake
with life style modifications recommendation
o Metformin is effective and safe, inexpensive and may
reduce the risk of cardiovascular event and death
o It may be safely used in patients with reduced eGFR
§ The FDA has revised the label for metformin to reflect
its safety in patients with eGFR of > 30 mL/min
• The selection of medication added to metformin is based on
patient’s preference and clinical characteristics
• Important clinical characteristic include:
o Presence of established atherosclerotic cardiovascular
disease (ASCVD)
o Other co-morbidities such as: heart failure or CKD
o Risk for specific adverse medication effects particularly
hypoglycemia and weight gain as well as safety tolerability PHARMACOLOGIC TREATMENT OF TYPE 1 DM
and cost
• Among patients with type 2 DM who has established ASCVD
o SGLT-2 inhibitor or GLP-1 receptor agonist with
cardiovascular benefit are recommended as part of
glycemic management

MANAGEMENT OF DIABETES MELLITUS

LIFESTYLE INTERVENTION
• Medical Nutrition Therapy (MNT)
o Hypocaloric diets and modest weight loss (5–7%) often
result in rapid and dramatic glucose lowering in individuals
with new-onset type 2 DM.
• Physical Activity
o 150 min/week (distributed over at least 3 days) of
moderate aerobic physical activity with no gaps longer
than 2 days
o Resistance exercise, flexibility and balance training, and
reduced sedentary behavior throughout the day are
advised.
• Psychosocial care
o Because the individual with DM faces challenges that affect
many aspects of daily life, psychosocial assessment and
support are a critical part of comprehensive diabetes care
MONITORING
• Self-Monitoring of Blood Glucose (SMBG)
o Standard of care in diabetes management and allows the
patient to monitor his or her blood glucose at any time. RELATIVE EFFECTS OF DIFFERENT INSULINS
o Short-term only
• HgbA1C
o long-term (every 3 months or every 6 months)
o Goal: as close to normal as possible without significant
hypoglycemia
o American Diabetes Association (ADA) recommends: <7%
PINGGANG PINOY
• Pinggang Pinoy is an easy-to-understand food guide that uses a
familiar plate model to convey the right food group proportions
on a per meal basis to meet the body’s energy and nutrient needs
of a Filipino adult
• It serves as visual tool to help Filipinos adapt healthy eating habits
• The shorter duration of action also appears to be associated with
at meal times by delivering effective dietary and healthy lifestyle
a decreased number of hypoglycemic episodes, primarily
messages
because the decay of insulin action corresponds to the decline in
• This is a 9-inch plate which is divided into 4 which is composed
plasma glucose after a meal.
primarily of:
• Basal insulin requirements are provided by long-acting insulin
o Carbohydrates
formulations (NPH insulin, insulin glargine, insulin detemir, or
o Proteins
insulin degludec). These are usually prescribed with short-acting
o Fruits
insulin in an attempt to mimic physiologic insulin release with
o Vegetables
meals
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PHARMACOLOGIC AGENTS USED FOR TREATMENT OF TYPE 2 DM • Insulin is sometimes the initial glucose-lowering agent in type 2
• The management of hyperglycemia in type 2 DM has become DM especially in patients who are in catabolic state
extraordinarily complex with the number of glucose-lowering
medications now available
• Advances in the therapy of type 2 DM have generated oral
glucose lowering agents that target different pathophysiological
processes of type 2 DM
• Based on their mechanisms of action, glucose lowering agents are
subdivided into agents that:
o Increase insulin secretion
o Reduced glucose production
o Increase insulin sensitivity
o Enhance GLP-1 action
o Promote urinary excretion of glucose
• Glucose-lowering agents other than insulin (with exception of
amylin analog), are ineffective in Type 1 DM and should not be
used in glucose management of severely ill individuals with Type
2 DM Essential elements in comprehensive care of type 2 diabetes

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• American Diabetes Association and European Association for the • Consider Insulin as first injectable if: (REMEMBER)
study of Diabetes with regards to the management of o HbA1C is >11%
hyperglycemia in type 2 Diabetes (refer to the figure above) o Symptoms or evidence of catabolism (weight loss, polyuria,
o New evidence for the benefit of specific medications to polydipsia)
reduce mortality, heart failure and progression of renal o If type 1 diabetes is a possibility
disease in the setting of established cardiovascular disease.
o Their use is considered compelling in this patient group METFORMIN
thus, they recommend that providers consider the history • The preferred initial pharmacologic agent for the treatment of
of cardiovascular disease very early in the process of type 2 diabetes
treatment selection. • Should be continued as long as it is tolerated and not
• Other factors affect the choice of medications particularly the contraindicated
setting of patient centered care, • Other agents, including insulin, should be added to metformin if
• In addition to cardiovascular disease, they recommend early glycemic control is above target
consideration of weight, hypoglycemic risk, treatment cause and
other patient related factors that may influence treatment SURGICAL THERAPIES FOR DM
selection. • Pancreatic and Kidney transplant
CHOICE OF INITIAL GLUCOSE LOWERING AGENT FOR T2DM o Whole pancreas transplantation can normalize glucose
control in type 1 Diabetes and when performed
Mild hyperglycemia Single, oral glucose-lowering agent
simultaneously with or after kidney transplantation:
(FPG 126-199 mg/dL)
Moderate hyperglycemia (FPG More than one oral agent or insulin
§ Can prolong the life of the kidney transplant by
200-250 mg/dL) offering protection against recurrent diabetic
Severe hyperglycemia Insulin therapy nephropathy due to the risks associated with chronic
(FPG 250 mg/dL) immunosuppresion.
HbA1C is ≥1.5% above Consider early combination therapy
individualized HbA1C target
• Pancreatic Islet Transplantation
HbA1C is still above target after Consider adding another agent o May be considered in patients with severe metabolic
reassessment instability or already requiring immunosuppression in
HbA1C is >10% or >2% above Consider initial injectable combination support of a kidney or other organ transplant
target (GLP-1 RA + basal insulin or
prandial/basal insulin)

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• Metabolic Surgery
o Considered in Type 2 DM and a BMI >30 kg/m2 if
hyperglycemia is inadequately controlled despite optimal
medical therapy
o This has shown considerable promise, sometimes with
dramatic resolution of the diabetes or major reductions in
the needed dose of glucose lowering therapies

ACUTE DISORDERS RELATED TO SEVERE HYPERGLYCEMIA

DIABETIC KETOACIDOSIS (DKA)

• Triad of:
o Hyperglycemia (≥ 250 mg/dL)
o Ketosis (β-hydroxybutyrate)
o Acidosis (serum bicarbonate <15mmol/L)
• Relative or absolute insulin deficiency combined with
counterregulatory hormone excess (glucagon, catecholamines, cortisol and
growth hormones)
• Most patients with DKA have autoimmune type 1 diabetes
however, patients with type 2 diabetes are also at risk due to the
catabolic stress of acute illness such as trauma, surgery or
infections
INITIAL EVALUATION OF DKA AND HHS
HYPERGLYCEMIC HYPEROSMOLAR STATE (HHS)
• Hyperglycemia (≥ 600 mg/dL), hyperosmolarity (>350
mosmol/L) PLUS dehydration in the absence of significant ketoacidosis
• Prototype: elderly individual with type 2 DM, with a several-week
history of polyuria, weight loss, and diminished oral intake that
culminates in mental confusion, lethargy, or coma
• Underlying Cause:
o Relative insulin deficiency
o Inadequate fluid intake

• Successful treatment of DKA and HHS requires:

Refer to the figure
• The events leading to hyperglycemia and ketoacidosis are
depicted.
• In DKA, reduced effective insulin concentrations and increased
concentrations of counterregulatory hormones lead to
hyperglycemia and ketosis
• The pathogenesis of HHS is not as well understood as that of DKA
but a greater degree of dehydration due to osmotic diuresis and
differences in insulin availability distinguish it from DKA.
• Although relative insulin deficiency is clearly present in HHS,
endogenous insulin secretion appears to be greater than in DKA
where it is negligible.
• Insulin levels in HHS are inadequate to facilitate glucose utilization
by insulin sensitive tissues but adequate to prevent lipolysis and
subsequent ketogenesis.
o Correction of dehydration
o Correction of hyperglycemia
o Correction of electrolyte imbalances
o Identification of comorbid precipitating events
o Above all, frequent patient monitoring
• Protocols for the management of patients with DKA and HHS are
summarized above
COMPLICATIONS OF DM
• Affect many organ systems
• Responsible for the majority of morbidity and mortality
associated with the disease
• Can be divided into vascular and nonvascular complications and
are similar in type 1 and type 2 diabetes
• The vascular complications of diabetes can be further subdivided
into microvascular and macrovascular

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 MICROVASCULAR MACROVASCULAR
1. Eye Disease 1. Coronary Heart Disease
o Retinopathy (non- 2. Peripheral Arterial Disease
proliferative/ 3. Cerebrovascular Disease
proliferative)
o Macular Edema
2. Neuropathy
o Sensory and Motor
(mono and polyneuropathy)
3. Nephropathy
o Albuminuria or
declining renal
function
• Microvascular complications are diabetes specific whereas
macrovascular complications have pathophysiologic features are
both shared with the general population and diabetes specific.

• Other Complications (Non-Vascular)

o Gastrointestinal (gastropareses/diarrhea)
o Genitourinary (uropathy/sexual dysfunction)
o Dermatologic
o Infectious
o Cataracts
o Glaucoma
o Cheiroarthropathy
o Periodontal disease
o Hearing loss

PHYSIOLOGY OF GLUCOSE COUNTERREGULATION

• In a cross-sectional survey of type 2 diabetic Filipino patients

diagnosed within 3 months or less from time of screening
o 20% already had peripheral neuropathy
o 42% of patients, proteinuria was seen
o 12% of patients had diabetic retinopathy.

HYPOGLYCEMIA
• Low blood sugar
• Potentially dangerous condition that is most common in people
with diabetes
• Happens when blood sugar drops to less than 70 mg/dL • When there is a drop in arterial blood glucose, a number of
• Most commonly caused by:
o Drugs used to treat Diabetes Mellitus mechanisms that normally prevent or rapidly correct
o Exposure to other drugs including alcohol hypoglycemia is activated
• However, a number of other disorders including critical organ • In insulin deficient diabetes, the key counterregulatory responses
failure, sepsis and inanition, hormonal deficiencies, non-beta cell such as suppression of insulin and increases in glucagon are lost
tumors, insulinoma, and prior gastric surgery may also cause and stimulation of sympathoadrenal outflow is attenuated
hypoglycemia
• May be documented by the Whipple’s triad

• Whipple’s triad
o Symptoms consistent with hypoglycemia
o Low plasma glucose concentration measured with a
precise method (<70 mg/dL)
o Relief of symptoms after the plasma glucose level is raised

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PHYSIOLOGIC RESPONSES TO DECREASING GLUCOSE • National Cholesterol Education Program: Adult Treatment Panel
REFER TO THE TABLE ABOVE III à the major features include: (REFER TO TABLE 401-1 page 11)
• There are certain physiologic responses to decreasing plasma o Central obesity
glucose concentrations o Hypertriglyceridemia
• The first defense against hyperglycemia or the primary glucose o Low levels of HDL
regulatory factor is a decrease in insulin o Hyperglycemia
• The second defense against hypoglycemia or primary glucose o Hypertension
counterregulatory factor is an increase in glucagon • 3 out these 5 criteria will confirm the diagnosis of metabolic
• The third defense against hypoglycemia which is critical when syndrome
glucagon is deficient is an increase in epinephrine
• An increase in cortisol and growth hormone are involved in
defense against prolonged hypoglycemia but they are not critical
ENDOGENOUS HYPERINSULINISM
• In the absence of any of the etiologic factors in a seemingly well
individual, the focus should shift to a possible endogenous
hyperinsulinism or accidental surreptitious or even malicious
hypoglycemia

• Diagnostic Criteria
1. Plasma insulin concentration ≥3 μU/mL (≥18 pmol/L)
2. Plasma C-peptide concentration ≥0.6 ng/mL (≥0.2
nmol/L) • As part of the metabolic syndrome, obesity which is a state of
3. Plasma proinsulin concentration ≥5.0 pmol/L excess adipose tissue mass is now a global epidemic
4. Plasma glucose concentration is <55 mg/dL (<3.0 mmol/L) • The prevalence of obesity, measured by Body Mass Index, has
5. Low plasma β-hydroxybutyrate concentration (≤2.7 alarmingly risen to unacceptable levels worldwide
mmol/L) and an increment in plasma glucose level of >25 • >1.9 billion adults worldwide are OVERWEIGHT
mg/dL (>1.4 mmol/L) after IV administration of glucagon • >600 million are OBESE
(1.0 mg)
• Obesity is associated with and contributes to:
o Shortened life span
• Prototype: Insulinoma
o Diabetes mellitus
TREATMENT OF HYPOGLYCEMIA o Cardiovascular disease
• If the patient is able and willing, oral treatment with glucose o Some cancers
tablets or glucose-containing fluids, candy, or food is appropriate o Kidney disease
o Initial dose is 15–20 g of glucose o Obstructive sleep apnea
o Gout
• Neuroglycopenia o Osteoarthritis
o If the patient is unable or unwilling to take carbohydrates o Hepatobiliary diseases among others.
orally à parenteral therapy is necessary
o IV glucose (25 g) should be followed by a glucose infusion
guided by serial plasma glucose measurements
o If IV therapy is impractical à SQ or IM
o IM glucagon (1.0 mg)
§ Particularly in patients with type 1 diabetes
§ Acts by stimulating glycogenolysis
§ Ineffective in glycogen depleted individuals

METABOLIC SYNDROME AND OBESITY

• Also known as Syndrome X or Insulin Resistance Syndrome

• Consists of a constellation of metabolic abnormalities that confer
increased risk of cardiovascular disease in diabetes mellitys
• It is estimated that around 20-25% of the world’s population have
metabolic syndrome and they are twice as likely to die from and
three times as likely to have heart attack or stroke compared with
people without the metabolic syndrome
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• Prevalence of Obesity in the Philippines • In patients whose BMI is 35 and above
o According to the Food and Nutrition Research Institute, o Pharmacotherapy is indicated but this can be given to
3 out of 10 Filipinos are overweight or obese patients with BMI 27 and above but with comorbid
o 27.6% of them are males and 34.4% are females conditions
• Bariatric surgery or Metabolic surgery
BODY MASS INDEX (BMI) o Necessary in patients whose BMI is 40 and above but can
be given to patients whose BMI 35 and above but with
Classification BMI (kg/m2) Risk of Comorbidities comorbid conditions
Underweight < 18.50 Low (but risk of
clinical problems
increased) USE AT YOUR OWN RISK
Normal Weight 18.50 – 24.99 Average
Overweight/ Pre-obese 25.00 – 29.99 Increased
Obese I 30.00 – 34.99 Moderate
Obese II 35.00 – 39.99 Severe
Obese III ≥40.00 Very Severe
• The National Institutes of Health and the World Health
Organization have both adapted BMI as a criterion for defining
obesity
• This made interpretation simpler and eliminated the need for sex
specific height or weight tables and provided a measurement
that is better correlated with other estimates of adiposity
• The measurement is based on the observation that body weight
is proportional to squared height in adults with normal body
frames
• In adults, classification systems and obesity guidelines define
healthy body weight as a BMI between 18.5-24.99 kg/m2

BMI FOR ASIAN POPULATION

Classification BMI (kg/m2) Risk of Comorbidities
Underweight < 18.50
Normal Weight 18.50 – 22.99 Increasing but
acceptable risk
Overweight/ Pre-obese 23.00 – 27.49 Increased risk
Obese ≥27.50 High risk

TREATMENT OF OBESITY

Treatment BMI Category (kg/m2)

25-26.9 27-29.9 30-34.9 35-39.9 ≥40
Diet, Exercise,
w/ w/
Behavioral + + +
comorbid comorbid
Therapy
Pharmacotherapy w/
- + + +
comorbid
Surgery w/
- - - +
comorbid

• The primary goals of treatment are:

o To improve obesity related comorbid conditions and
o Reduce the risk of developing future comorbidities
• For patients who are overweight, diet, exercise, and behavioral
therapy are necessary

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