The key to longevity in trying to live with Diabetes is in precise management and that is hindered by meds with side effects or lack of awareness among patients or it could be lack of everyday patient compliance

1. Diabetes Management
The Medication Conundrum

2. The Glycemic Imbalance
Diabetes is a disease in humans that
causes blood glucose (sugar) levels to rise
and remain higher than normal
While multi-factorial in cause, when
simply put this is typically caused either
because
(1) The pancreas does not produce
enough insulin
(2) The Cells are glucose intolerant
(3) Ineffectiveness of Insulin due to
elevation of cortisol levels brought by
stress (esp; long term)

3. Available Medications*
http://www.diabetes.org/living-with-diabetes/treatment-and-care/medication/oral-medications/what-
are-my-options.html
* Injectables like Insulin while routinely preferable are not mentioned

4. Adverse Effects for Available Medications

5. The Conundrum
• Diabetes is a known leading cause of such morbidities as
cardiovascular disease, premature blindness, kidney failure,
neuropathy and peripheral gangrene leading to limb amputation.
People with diabetes have a intrinsic higher risk of developing
infections leading to further complications. Consistently high
blood glucose levels is the main factor across all such seen issues
• Maintaining blood glucose levels can help to delay or prevent
further diabetes complications. It is therefore imperative that
people with diabetes understand the need for regular monitoring
• Available Oral medications are only as effective with their own
problems in usage, but Newer methodologies and devices are
allowing for better tracking/ monitoring
• The problems facing effective management
– Current medications are many with unfortunate side effects for most, not
personalized
– Lack of awareness leads to challenges in holistic management
– Lack of everyday patient compliance an issue for precision and effectiveness

6. How do Sulphonylureas work?
Sulphonylureas are insulin secretagogues, which means they work by causing the body to secrete
insulin.
Another class of diabetes drugs which works in this way is the prandial glucose regulators class.
Sulphonylureas bind to a channel of proteins in the pancreas (ATP-sensitive potassium channel).
This triggers a sequence of events within the cells that leads to an increase in the amount of insulin that
is produced by pancreatic beta cells.
The primary benefit of sulphonylureas is their effect on increasing insulin secretion and therefore
helping to reduce blood glucose levels.
Sulphonylureas are not recommended for people who are overweight or obese, as their mode of action
(increase in insulin production and secretion) means that weight gain can be a relatively common side
effect.
Their effect on insulin levels also means users are at increased risk of hypoglycaemia (low blood sugar),
although this risk is reduced with newer sulphonylureas such as glimepiride.
In addition, some users may suffer an allergic reaction during the first six weeks to eight weeks of
treatment, resulting in itchy red skin/skin rashes. If this happens, you might need to switch to another
anti-diabetes drug.
https://www.diabetes.co.uk/diabetes-medication/sulphonylureas.html

7. What about SGLT2 Inhibitors?
SGLT2 inhibitors are called gliflozins. They lead to a reduction in blood glucose levels. Therefore, SGLT2
inhibitors have potential use in the treatment of type II diabetes. Gliflozins enhance glycemic control as well
as reduce body weight and systolic and diastolic blood pressure.[7]
The gliflozins canagliflozin, dapagliflozin,
and empagliflozin may lead to euglycemic ketoacidosis.[8]
Other side effects of gliflozins include increased
risk of (generally mild) genital infections, such as candidal vulvovaginitis.[9]
Phlorizin is an inhibitor of SGLT1 and SGLT2. With phlorizin as lead compound, specific inhibitors of SGLT2
were developed in the last decade and some of them have been approved for treatment mainly of type 2
diabetes. Inhibition of SGLT2 eliminates excess glucose via the urine.
Gliflozin drugs are a class of medications that inhibit reabsorption of glucose in the kidney and therefore
lower blood sugar.[1]
They act by inhibiting sodium-glucose transport protein 2 (SGLT2), and are therefore
also called SGLT2 inhibitors. Gliflozins are used in the treatment of type II diabetes mellitus (T2DM). Apart
from glycemic control, gliflozins have been shown to provide significant cardiovascular benefit in T2DM
patients.[2]
Several drugs of this class have been approved or are currently under development.[3]
In studies
on canagliflozin, a member of this class, the drug was found to enhance blood sugar control as well as
reduce body weightand systolic and diastolic blood pressure.[4]
Phlorizin is found primarily in unripe Malus (apple),[2]
root bark of apple,[3]
trace amounts have been found
in strawberry.[4]
In Malus, it is most abundant in vegetative tissues (such as leaves and bark) and seeds.
Closely related species, such as pear (Pyrus communis), cherry, and other fruit trees in the Rosaceae do not
contain phloridzin.[5]
Phloridzin is a phytochemical that belongs to the class of polyphenols. In natural
sources, it may occur with other polyphenols such as quercetin, catechin, epicatechin, procyanidins,
and rutin
https://en.wikipedia.org/wiki/SGLT2_inhibitor

8. Link between GLP-1 and Insulin Secretion?
β
β
β
In hyperglycaemic Type 2 diabetic patients, ingestion of acarbose with a mixed test meal failed to
enhance GLP-1 release and did not influence gastric emptying.
https://www.ncbi.nlm.nih.gov/pubmed/15787675

9. Rationale for Dipeptidyl Peptidase-4 Inhibitor
Glucagon increases blood glucose
levels, and DPP-4 inhibitors reduce
glucagon and blood glucose levels.
The mechanism of DPP-4 inhibitors
is to increase incretin levels (GLP-1
and GIP),[2][3][4]
which inhibit
glucagon release, which in turn
increases insulin secretion,
decreases gastric emptying, and
decreases blood glucose levels.
A 2018 meta-analysis found no
favorable effect of DPP-4 inhibitors
on all-cause mortality, cardiovascular
mortality, myocardial infarction or
stroke in patients with type 2
diabetes.[

10. Insulin Resistance and TZDs
Thiazolidinediones—sometimes shortened to TZDs or glitazones—work on lowering your
insulin resistance, which is the underlying problem for many people with type 2 diabetes.
TZDs make your body produce new fat cells, and those cells are actually more sensitive to
insulin—that is, they allow insulin to do its job. If you’re insulin resistant, your cells don’t
allow insulin to do its job (which is to get glucose into the cells). The new fat cells, then,
can eventually lower your blood glucose level by making your body use insulin and
glucose better.
NOTE: The first-generation thiazolidinediones actually caused serious liver damage in a
few people. The second-generation TZDs shouldn’t do that, but it’s still something to
keep in mind, especially if you already have liver problems.
https://www.endocrineweb.com/conditions/type-2-diabetes/thiazolidinediones-tzds-or-glitazones-
type-2-diabetes

11. The Glycemic Control Algorithm
https://www.aace.com/sites/all/files/diabetes-algorithm-executive-summary.pdf

12. Need Of The Hour
• The key to longevity in trying to live with
Diabetes is…Precise Management, and
we @ QUAHOG have the key!

13. Quahog Life Sciences is working to optimize the diabetic insights and
management routines by way of bringing together all relevant data sources to
predict and recommend, in order to manage blood sugar efficiently
Quahog becomes a centralized decision engine by connecting to all data sets. The app
collects data explicitly from patients with regard to food, meds, stress related behavior
along with other conditions like cholesterol. Along with this data, it integrates data from
external apps that track sugar, burn and from insulin pens.
Users can keep a constant watch for hypoglycemic complications, weight changes,
ketoacidosis or factors affecting kidney, gastrointestinal tract, bones, and the heart.
It can be personalized based on different user types where patients could be Pre-diabetic
or Diabetic -managed by meds or Diabetic-managed by meds and insulin

14. Predictions help to plan strategies for any imbalance
Once all available data is thus unified, we can better
• Predict sugar values for the next 24 hrs based on past patterns
Based on past behavioral and outcome patterns, we can predict sugar values and propose strategies (from past
patterns) that can bring the sugar levels back in range
• Recommend Food before meals with calculated sugar
Based on sugar status and past meal history, we can recommend foods that best suit the profile, and help user
stay within the range
• Recommend Workouts with calculated burn
Based on BMI , sugar count, and required BMR, we can recommend work-outs that allow in better management
of sugar
• Understand which strategy is effective through attribution
Knowing which strategy is working for the patient is crucial. Using a probabilistic attribution, we can arrive at
the effectiveness of each strategy and propose the right strategic combination
• Plan Medicine or Insulin Dosage for effective management
With data available on regular basis, it will be useful to plan medication and also find ways to reduce dosages

15. Why we can better manage sugar levels
• Ability to compute real-time data
As the system can compute in real-time, any data inputs collected across sources, are quickly computed to get
net weights. The data model allows in causal analysis helping in understanding the cause behind the sugar level
This allows in reasoning and managing scenarios instantly
• Ability to predict
Based on multiple dimensions, the system can predict sugar levels. This should help us a great deal in managing
next meal or medication and avert any risk that can accumulate, helping in better management.
• Ability to work on diet at a granular level
Working on diet to its granular level can make way for better control across strategies. Diet plays an important
role not only in managing sugar but also other factors like cholesterol, weight gain and others. Using diet as a
marker allows in optimizing intake, which has a cascading effect on all strategies. Controlled diet and workouts
can make a big difference in managing sugar
• Ability to learn from successful patterns (positive outcomes)
The app also has reference of patterns that resulted in positive outcomes among certain users,. Such patterns
can be referred for working better strategies for users, who belong to the identical segment for better results
• Ability to keep the doctor informed
The app constantly checks for sugar levels and can alert the associated doctor whenever the levels go out of
range. Doctor can immediately prescribe or recommend actions over the app so it gets back into range.
Allowing the doctor to view patterns of past behavior will allow them to strategize better and measure the
outcomes of the prescribed strategies