Chronotherapy is an approach to diabetes treatment that involves timing medication administration relative to a patient's circadian rhythms. Insulin secretion and sensitivity exhibit daily rhythmicity controlled by the circadian clock, and disrupting these rhythms can lead to impaired glucose metabolism and diabetes. Studies have found higher post-meal blood glucose levels in the evening compared to the morning, even after identical meals. Chronotherapy aims to optimize drug effects and safety by administering medications, like insulin and sensitizers, in line with a patient's circadian rhythms. This personalized timing of treatment can help improve glycemic control while reducing risks like hypoglycemia.

1. CHRONOTHERAPY OF
DIABETES
Presented By :- Suhas M. Patil
Roll no :- MPL 12
F.Y M. Pharm
Department Of Pharmacology
R. C. Patel Institute of Pharmaceutical Education & Research Shirpur (M.S.)
Guided By :-
Mr. M. B. Gagarani

2. CONTENTS
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 Introduction
 Types of DM
 Chronopharmacology
 Circadian rhythms, Insulin action & Glucose homeostasis
 Circadian clock controls
 Blood Glucose and the Circadian Rhythm
 Eating, Sleeping and Shift Work
 Chronotherapy of diabetes
 Ideal characteristics of Chronotherapy
 Advantages & Disadvantages
 References

3. INTRODUCTION
 Defination :- Diabetes is a disease that occurs when your blood glucose, also
called blood sugar, is too high. Blood glucose is your main source of energy and
comes from the food . Insulin, a hormone made by the pancreas, helps glucose
from food get into your cells to be used for energy
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4. Sign & Symptoms :-
 Increased Thirst
 Frequent Urination
 Unexpected Weight Loss
 Blurred Vision
 Increased Fatigue
 Numbness & Tingling (in feet & hands)
 Tender Gums
 Slow Healing Sores
 Red Swollen 4

5. Obesity
History of CVD Hypertension
Physical Inactivity
Family HistoryPolycystic Ovarian Syndrome

6. Types of Diabetes Milletus
TYPE II
DM
NIDDM
TYPE I
DM
IDDM
TYPE III
DM
GESTATIONAL
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Chronopharmacology Science dealing with optimization of drug effects &
minimization of adverse effects by timing medications in relation to biological
rhythm. It is concerned with the effects of drugs upon the timing of biological
events and rhythms.
Chronobiology :- The branch of science focusing on biological rhythms and
their mechanisms.
Chronos (time),
Bios (life),
Logos (study).
Chronopharmacology

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Biological rhythm :-
The physiological parameters shows a rhythmic change, mostly synchronized with
the periodic changes in the environment.
Circadian : Lasting for about 24 hours. -Sleep wake cycles
Infradian: Cycles longer than 24 hours. -Menstrual cycle
Ultradian: Cycles shorter than a day. -Neuronal firing time
Seasonal: Seasonal affective disorders.

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Biological Clock- It’s a natural mechanism of oraganism which change on
daily, seasonal, yearly or other regular cycle

10. “
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CHRONOPHARMACOLOGY SUBDIVIDED
CHRONOTHERAPY
CHRONESTHESY
CHRONOTOXICITY
CHRONOPHARMACOKINETIC

11. Circadian rhythms, Insulin action & Glucose homeostasis.
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Disturbed Circadian Rhythms
 Caused by exposure to light at night
 Associated with lower nocturnal
melatonin
 In turn affects to glucose
metabolism
 Increase insulin resistance and
decrease pancreatic function
 Gene Clock polymorphism or altered
expression of clock gene
 Play role in development of obesity
and diabetes in human

12. Circadian clock control sugar metabolism(1)
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 Researchers of Boston have found that the human glucose tolerance is reduced
during evening that day and night because the circadian rhythm
 People who work at night shift are more prone to type-2 Diabetes and obesity
 The study was performed by Scheer & his colleagues on 14 healthy
individuals mimicking the day & night shift work pattern
 It showed 17% higher glucose levels (including lower glucose tolerance) in
the evening than in the morning

13. Circadian Clock Controls Insulin and Blood Sugar in Pancreas
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 A new Northwestern Medicine study
 The genetic pathways an internal body clock takes to dictate how and when our
pancreas must produce insulin and control blood sugar
 And finally findings that the new therapies for children and adults with diabetes
 The body’s circadian clocks co-ordinate behaviours like eating and sleeping, as well as
physiological activity like metabolism, with the Earth’s 24-hour light-dark cycle
 There’s a master clock in the brain as well as peripheral clocks located in individual
organs
 When genetics, environment or behaviour disrupt the synchrony of these clocks,
metabolic disorders can develope

14. Blood Glucose and the Circadian Rhythm(1)
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 Endocrinologists and other health professionals work with diabetic patients
 They have long been aware that blood glucose levels vary with the time of day, even
independently of eating habits and insulin use
 Many people with diabetes experience what is known as a dawn phenomenon, in which
the liver releases large amounts of glucose into the bloodstream just before dawn
 The blood sugar can be as much as is contained in two cans of regular soda.
 This can cause problems for people with diabetes that is difficult to manage.
 In addition, diabetics are advised not to eat high carb meals late at night, as this often
causes higher blood glucose levels than the same foods would cause at other times of the
day

15. Eating, Sleeping and Shift Work(1)
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 According to this study a group of people lived under laboratory conditions that
were rigidly controlled
 Then for eight days study participants had a normal daily rhythm with breakfast
in the morning, dinner in the evening and sleep at night
 This schedule was then reversed for four weeks
 The participants ate breakfast in the evening, worked all night, ate dinner in the
morning, and slept all day.
 Blood glucose levels were tracked throughout the experiment, with surprising
results.

16. Cont…
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 Post-meal blood glucose levels were higher by 17 percent in the evening than in
the morning, even after identical meals
 This occurred regardless of what shift the study participant’s worked
 It’s Not Just What You Eat, but when this new information offers a possible
explanation for the fact that shift workers are more likely to develop diabetes
 Breakfasts are higher in carb content than dinners in the Western world; eating this
type of meal in the evening can lead to sustained blood sugar fluctuations that
eventually cause insulin resistance

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 Both insulin secretion by pancreatic cells and insulin sensitivity in the insulin
target organs shows daily rhythmicity
 It may be involved in maintaining homeostasis of glucose metabolism.
 Because these rhythms are impaired in patients with diabetes, the correction of
these abnormalities is necessary for effective treatment
 There are few studies showing chronotherapy of insulin sensitizers
(thiazolidinediones and biguanides)
Chronotherapy of diabetes
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18. Cont…
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 The medications which are used for the treatment of impaired insulin secretion, including
glinides and rapid- and long-acting insulin analogs, have the merit of chronotherapeutic
approach
 These medications are useful not only for improving glycemic control but for the risk
reduction of prolonged hypoglycemia and body weight gain.
 It showed that circadian clock is impaired in patients with type 2 diabetes
 Because the association between clock gene expression and glucose tolerance is also detected
in subjects without diabetes, favorable lifestyles (e.g. awake time, bedtime, drinking) to
maintain circadian clock function are important for the prevention of type 2 diabetes

19. Ideal characteristics of Chronotherapy
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 Non‐toxic within approved limits of use.
 Should have a real‐time and specific triggering biomarker for a given disease state.
 Should have a feedback control system
 Biocompatible and biodegradable, especially for parenteral administration.
 Easy to manufacture at economic cost.
 Easy to administer into patients in order to enhance compliance to dosage regimen

20. Advantages of Chronotherapy
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 Chronotherapy is drug-free
 It is more effective when a person sleeps for several hours
 While Chronotherapy patients often fall asleep this improves their condition and
confidence as well
 It is different from other treatments because it got the beginning, middle, and an
end. So one can predict easily the point at which it will work
 It gives a new schedule like getting up and sleeping early which will be quite
unusual for some days but it will give a period to adjust psychological

21. Disadvantages of Chronotherapy
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 It develops a non 24 hours sleep wake syndrome after the treatment as the person
sleeps for over 24 hours during the treatment. It’s not quite common but the degree
of risk is not known.
 Person may also be deprived of sleep sometimes.
 Person becomes less productive during chronotherapy and staying awake till the
other schedule might be bit uncomfortable.
 Person will have to take some time off from your busy normal schedule as its time
taking therapy.

22. Cont…
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 Medical supervision is mandatory for this therapy and regular consulting of sleep
specialists is recommended
 Person has to keep himself awake till the next sleep schedule so he has to get
himself busy so that he stay awake till the other schedule
 Person undergoing therapy may feel unusually hot or cold sometimes
 Patient needs to consult the doctor regularly to avoid side effects

23. Reference
 Sagar, A. and Jough, S., Chronopharmacology: Recent Advancements in the
Treatment of Diabetes Mellitus through Chronotherapy
 Chronopharmacology & its Aspects , www.pharmainfo.net
 K.D. Tripathi “Essential of medical pharmacology Jaypee brothers medical
publishers (P) LTD

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