DR ANIMESH PAUL

LEARNING OBJECTIVES
• Definition
• Epidemiology
• Pathogenesis
• Secondary Forms of Diabetes and Hypertension
• Screeing and Evaluation
• Target to achieve
• Management
• Special Situations
• CASE 1. Mrs. Kamala (53yrs/F) has been
coming regularly for follow-up of Type 2
diabetes.Her BP found to be 144/90 mm
Hg.

• CASE 2. Mr. Kishor (48yrs/M) has

diabetes for 10 years and hypertension for
5 years.
• He is irregular in treatment. He is also a
heavy smoker. He has now presented for
swelling of his feet. His BP is 160/100 mm
Hg.
 INTRODUCTION
• Diabetes mellitus (DM) and hypertension are the two important lifestyle
disorders affecting a large number of population in the Indian
subcontinent and globally.
• They have overlapping pathophysiological mechanism often referred to
as “common soil theory”.
• The common risk factors for both the disorders are obesity, insulin
resistance, dyslipidemia, metabolic syndrome.
• More than 50% of patients diagnosed with hypertension in India have
concomitant type 2 diabetes
• People with T2DM showed 1.5-2.0 times higher prevalence of
hypertension than those without diabetes.
• Diabetes is associated with various vascular complications and
associated systemic hypertension can increase the risk of heart failure
(HF), chronic kidney disease (CKD), peripheral artery disease (PAD),
cardiovascular disease (CVD) by many folds.
 DEFINITION
• Blood Pressure(BP) refers to the pressure wave in the arterial wall
when the heart contracts (SBP) and when heart relaxed(DBP).
• Hypertension in the general population(JNC8) is defined as a BP
above or equal to 140/90 mm Hg.
• The American Diabetic Association (ADA) also had recommended
a BP below or equal to 130/80 mm Hg as the target BP for patients
with diabetes.
• The JNC 8 committee (2014) however has revised to a target BP
below140/90 mm Hg have been accepted as a reasonable target
irrespective of the presence or absence of diabetes.
 EPIDEMIOLOGY
GLOBAL SCENARIO
• In type 1 diabetes, hypertension
• Globally an estimated 462 million occurs at the onset of
individuals affected by T2 DM nephropathy. The incidence
corrosponding to 6.28% of world’s rises from 5% at 10 years to
population with highest prevalance 33% at 20 years and 70% at 40
years, and closely related to the
in China, India, US, Indonesia and
onset of microalbuminuria and
Mexico.
progression of renal disease.
INDIAN SCENARIO
• In India 74 million people living
• In type 2 diabetes, more than
with diabetes with prevalance of
50% of patients have
7.7% in 2016.
hypertension even at the time
• Highest in Tamilnadu, Kerala,
of diagnosis of diabetes.
Delhi, Punjab, Goa.
 PATHOPHYSIOLOGICAL MECHANISM OF
HYPERTENSION IN DIABETES
A common pathophysiological mechanism contributes to the occurrence/
exacerbation of diabetes and hypertension.
1. INSULIN RESISTANCE
Receptor-specific resistance prevents the favorable effects of insulin like
glucose utilization, lipid metabolism, and endothelium-dependent
vasodilatation (nitric oxide pathway) are defective.
On the other hand unfavorable effects of insulin like sodium retention,
activation of the sympathetic nervous system, vascular smooth muscle cell
(VSMC) proliferation and cytosolic calcium deposition, and enhancement of
vascular lipid deposition all progress unchecked.

2. SYMPATHETIC NERVOUS SYSTEM

Increase activity which results in increased circulating norepinephrin level.
3. SODIUM AND WATER RETENTION
Insulin promotes renal tubular reabsorption of sodium via the direct
stimulation of the Na/H antiport system or the Na, K-ATPase in the renal
tubule.
4. RENIN ANGIOTENSIN ALDOSTERONE SYSTEM (RAAS)
Activation of the RAAS results in unregulated angiotensinogen Il activity
through its AT1 receptor leading to the formation of reactive oxygen
species (ROS).
5. SODIUM LITHIUM COUNTER TRANSPORTER
Red blood cell (RBC) Na/Li counter transport reabsorbs sodium in the
proximal tubule, has been found to be overactive in those with diabetes
and hypertension. First-degree relatives of patients with diabetic
nephropathy also display increased activity of Na/Li counter transport.
6. GENETIC FACTORS
Missense mutation of the Beta-adrenergic receptor gene (ADRB3) is
associated with low resting metabolic rate, weight gain, early onset of type
2 diabetes, and hypertension.
7. HYPERGLYCEMIA
Glycosuria stimulates fluid and sodium reabsorption through the proximal
tubule sodium-glucose cotransporters. Hyperglycemia-associated protein
glycation can lead to arterial stiffness.
 SECONDARY DIABETES AND HYPERTENSION
5-10% subjects with hypertension have a potentially correctable secondary
cause.
DRUGS: ENDOCRINE
• Nasal decongestants
• Acromegaly
• Glucocorticoids
• Cushing Syndrome
• Tricyclic antidepressants,
Sibutramine, • Pheochromocytoma
• Amphetamine, Cocaine, • Primary Hyperaldosteronism
• Oral contraceptives • Primary Hyerparathyroidism
• Hypothyroidism
RENO VASCULAR: • Hyperthyroidism
Two most common primary • Polycystic ovarian syndrome
diseases are atherosclerotic renal • MEN Syndrome
artery stenosis (ARAS) and • Autoimmune Polyglandular
fibromuscular dysplasia (FMD). Syndrome
WHEN TO SUSPECT SECONDARY CAUSE
 SCREENING AND EVELUATION
• Accurate measurement of BP is key factor. Average of two or more
proper measurements on each of two or more office visits is taken.
• Office BP measurement performed either through the auscultatory
technique of listening to Korotkoff sounds or the oscillometric technique
employed in automated devices.
• Patient’s posture should be proper and appropriate size cuff should
be used with a proper caliberated instrument.
• Ambulatory blood pressure monitoring (ABPM) measures BP for a period
of 24-hours.
• Compared to office blood pressure measurement, ABPM has higher
prognostic value for target organ damage and cardiovascular
outcomes. It also detects distinct blood pressure patterns such as
white-coat, masked, and nocturnal hypertension, as well as non-
dipping (more prevalant in diabetes) or reverse-dipping patterns that
cannot be detected with office measurements alone.
 TARGET BLOOD PRESSURE IN DIABETES
• ADA Suggests In patients
with diabetes and
hypertension target should
be < 130/80 mm Hg if can be
achieved with out any side
effects.
• Blood pressure < 125/75
mmHg are recommended for
people who have proteinuria
>1gm/day and renal
insufficiency regardless of
aetiology.
Target Blood Pressure <130/80 vs <140/90 which one is more suitable?
• A large meta-analysis of randomized trials comparing intensive BP control
(<130/80 mmHg) v.s. the new standard target (< 140/90 mmHg) did not
show any difference in mortality or in instances of non-fatal MI, with
absolute risk reduction was only 1% with relation to strokes. The same
analysis also revealed intensive control was associated with increased
adverse events like syncope and hypotension.
• Two large trials on blood pressure control in patients with diabetes, Firstly
the ACCORD trial targeted a blood pressure of 120/70 mmHg (average
BP 119/64 using an average of 3.4 drugs) which showed no benefits
Mortality, non-fatal MI and non-fatal strokes despite the extra costs and
effort.
• On the other hand the ADVANCE-BP trial showed significant
reductions in macrovascular and microvascular endpoints as well as
all-cause mortality with the use a single pill combination of an ACEI and
a thiazide with a average blood pressure of 136/73 mmHg.
NONPHARMACOLOGIC THERAPY OF HYPERTENSION

• A decrease in the daily total salt intake can reduce SBP by 5 mm

Hg and DBP by 3 mm Hg.
• Weight reduction has been shown to lower the need for
medications (1 kg weight loss accounts for 1 mm Hg
fall in BP).
 PHARMACOTHERAPY OF HYPERTENSION
• ACE inhibitors or ARBs as the first-line treatment agents for diabetic
hypertensive patients. Other therapeutics options, such as calcium
channel blockers (CCBs), beta-blockers, and diuretics can be used.
• Many evidences suggest that single-pill combination (SPC) or fixed-
dose combinations containing two or more anti hypertensive agents with
the complimentary mechanism of action have more advantages than
using free drugs.
• Telmisartan and Losartan have shown to reduce cardiovascular events
and risk factors.
• Telmisartan must be chosen over other ARBs in patients with
diabetes because of its beneficial effect on fasting blood glucose and
serum insulin levels.
• Losartan is preferred in patients with diabetes with a higher risk of
stroke.
• Azilsartan is a suitable agent as antihypertensive therapy in diabetes
with CKD.
• Cilnidipine is a novel and unique dihydropyridine CCB with
inhibitory actions on both L-type and N-type calcium channels. It
prevents arterial fibrillation by reducing the intracellular calcium
load and has lesser chances of pedal edema.
• Hydrochlorothiazide has predominant effect on systolic BP, reduce
the pulse pressure by 4-6 mmg. Thiazide-like diuretics have shown
good BP reduction in patients with resistant hypertension.
• Thiazide-like diuretics have potential effect on worsening
glycemic status and, hence, less preferred in patients with
diabetes. However, the low doses of thiazide diuretics might have
lesser effect on glycemic changes. Hyponatremia, especially in
eldety population with diabetes and hypertension, is a concern.
• Potassium-sparing diuretics such as spironolactone have shown
its beneficial effect in resistant hypertension.
 DIABETES AND HYPERTENSION MANAGEMENT IN SPECIAL
SITUATION

PREGNANCY:
• Hypertensive disorders complicate 5-10% of all pregnancies and 20% of
pregnant women with Diabetes.
• Chronic Hypertension and pregnancy trial(CHAP) suggest target BP
should be 110-135/85 mmHg.
• Anti Hypertensive can be given in pregnancy are Nifedipine, Dilteazam,
Labetolol, Clonidine, Prazosin.
• Low dose aspirin 100-150mg/day should be added to pregnant Type 1
and 2 diabetes women at 12-16 week of POG to lower the risk of Pre-
eclempsia.
TYPE 1 DIABETES
Adolescent(≥13 years)
• Normotensive < 120/<80 mmHg
• Elevated BP 120/<80 to 129/<80 mmHg.
• Stage 1 HTN 130/80 to 139/89 mmHg : Life Style modification and
intensive workup.
• Stage 2 HTN ≥ 95th percentile+ 12 mm Hg or ≥140/90
mmHg( Whichever is lower) : Pharmacologic treatment. ACEI/ARB
firstline. CCB and Diuretics added as second line.
ELDERLY PATIENTS WITH DIABETES AND
HYPERTENSION
• Little information is available regarding the target BP levels in elderly
hypertensive patients with T2DM.
• Intensive HTN treatment in the elderly patients increases the risk of
hypotension, syncope, and possibly falls particularly in frail
individuals and chronic kidney disease (CKD) patients.
• Target BP should be based on concomitant diseases, orthostatic BP
changes, and the general condition of the patients.
• A practical target BP for the elderly patients with diabetes is < 130/80
mmg for most but for those with limited life expectancy, advanced
stages of heart failure, CKD requiring dialysis, severe cognitive
impairment and/or severe limitation in the activities of daily living
(ADL), target BP of <140/90 mmHg is suggested.
 HYPERTENSION AND DIABETIC KIDNEY DISEASE

ADA and KDIGO recommends

ACEI and ARBs at highest
tolerated dosages as the initial
therapy.
Non DHP CCBs like Verapamil
and Dilteazam can serve as
1st line who are intolernt to
ACEI/ARB.
 LABILE HYPERTENSION AND AUTONOMIC
DYSFUNCTION
• Uncontrolled DM can lead to Cardiac autonomic Neuropathy which
can cause
1. Orthostatic Hypotension
2. Supine Hypertension
3. Labile Hypertension.
• Diagnosed by Clinical Examination, ABPA, Cardiovascular autonomic
reflex testing(CART).
• Management:
1. Optimal glycemic Control
2. Avoid autonomic stressors
3. Compression stockings
4. Physical maneuvers
5. Drug which affects by antagonizing Sympathetic activity( alpha/beta
blockade like Carvedilol, Labetolol)
 ANTI DIABETIC AGENTS IN PATIENTS WITH
COMBINED HYPERTENSION
• Insulin, Sulfonylurea, Glinides has no impact on BP.
• Metformin slightly decrease BP in people with hypertension but not in
a clinically meaningful way.
• PPAR gamma agonist slightly lowers SBP but increases the incidence
of HF
• Alpha Glucosidase inhibitors decrease both SBP and DBP and
lowers the risk of new episode of hypertension.
• DPP 4 inhibitors (Sitagliptin, Vildagliptin) has modest decrease in in
SBP and DBP (1.5 to 3 mmHg)
• Oral GLP1 agonist (Semaglutide) has effect on reduction og BP.
• SGLT2 inhibitors decreases 4-6 mmHg of SBP and 2-3 mmHg of DBP.
 SUMMARY OF ADA 2024 RECOMMENDATIONS FOR
HYPERTENSION IN DIABETES

• Blood pressure should be measured at every routine clinical visit.

• All people with hypertension and diabetes should be counseled to
monitor their blood pressure at home
• For people with diabetes and hypertension, blood pressure targets
should be individualized
• The on-treatment target blood pressure goal is <130/80 mmHg, if it can
be safely attained.
• In pregnant individuals a blood pressure threshold of 140/90 mmHg for
initiation or titration of therapy with a blood pressure target of 110–
135/85 mmHg
• For people with blood pressure >120/80 mmHg, lifestyle intervention.
• Individuals with confirmed office based blood pressure 130/80 mmHg
initiation and titration of pharmacologic therapy.
• Individuals with confirmed office based blood pressure 150/90 mmHg
should have prompt initiation and titration of two drugs or a single-pill
combination.
• ACE inhibitors or ARBs are recommended first-line therapy and
should not be combined.
• An ACE inhibitor or ARB, at the maximum tolerated dose in Albuminuria
patients( ACR≥300mg/gm)
• Patients started with ACEI,ARB, MRA or diuretic, serum creat, serum
K+levels should be monitored within 7–14 days after initiation of
therapy and at least annually.
• CASE 1. Mrs. Kamala (53yrs/F) has been coming
regularly for follow-up of Type 2 diabetes. Her BP
found to be 144/90 mm Hg.

• Start lifestyle modifications: Moderate salt intake, weight

reduction (if overweight), regular, moderate exercise.
• Antihypertensive drugs: Her initial BP is > 10 mm but < 20
mm above the target; so she needs both lifestyle
modifications as well as drug therapy, starting with a single
drug.
• CASE 2. Mr. Kishor (48yrs/M) has diabetes for 10 years
and hypertension for 5 years. He is irregular in
treatment. He is also a heavy smoker. He has now
presented for swelling of his feet. His BP is 160/100 mm
Hg.

• Common D/Dx would be Heart failure, Diabetic Kidney

disease.
• ACE inhibitors and diuretics for the control of symptoms
and hypertension.
• Further evaluation into the cause and Glycemic control.
THANK YOU