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                            Humihealth. blogspot.com

                            Medical Matters

                                          by

                                P.K. Ghatak, MD.

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                                   Index II 

     226                 5/16/2025         The Last Blog

     225                 3/10/2025         Laser

     224                 3/06/2025          Endoscope      

     223                2/22/2025          Use of Ultrasound in Medicine

    222                 2/05/2025           MRI                  

    221                 1/1/04/2025       Bacteriology & Robert Koch  

    220                  1/17/2025         Vaccination and Edward Jenner                               

   219                  1/04/2025          Plague

   218                  12/03/2024         Leprosy

   217                  11/30/2024         Syphilis

  216                   11/15/2024         Subacute Combined Degeneration of the Spinal Cord.

  215                   11/03/2024         Hodgkin Lymphoma.

  214                   10/28/2024         Peripheral Neuropathy.

 213                   10/14/2024          Septicemia and Sepsis.  

 212                   10/10/2024          Syndrome in Clinical Medicine.                

 211                   09/28/2024          Cysts.

 210                   09/10/2024          Ophthalmic Migraine

209                    09/14/2024          Kennedy's Disease and MND                                                           

208                    06/30/2024            Jaundice                                           

207                   06/18/2024             Situs Inversus

206                   06/ 05/2024            Changing Concept of Crohn's Disease.

205                   05/06/2424             Pain Perception.

204                   05/ 02/ 2024           Urinary incontinence

203                   04/07/2024             Whipple's disease          

202                   04 / 03 /2024          Stories Nails Tell

201                   03/20/2024             Heart Failure

200               03/17/24              Toxoplasma gondii

199                 03/14/24            Burkitt Lymphoma Virus  

198                 03/11/24            Chickenpox

197                 03/6/24              Cytomegalovirus

196                     02/17/24               Prion Diseases                                                       

195                02/16/24              Prion

Number	Date	Title
194	02/09/24	Pneumocystis jirovicii pnemonia
193	02/09/24	Amoebiasis
192	02/05/24	Giardiasis
191	02/03/24	Whipworm infection
190	01/03/24	Tapeworm disease
189	12/11/23	Blood Flukes
188	12/06/23	Ascaris lumbricoidis
187	12/04/23	Hookworm
186	12/01/23	Lung Flukes
185	11/28/23	Fasciola Hepatica
184	11/25/23	Oriental Sores
183	11/21/23	Chagas Disease
182	11/14/23	Dracunculiasis
180	11/13/23	Elephantiasis & Tropical Eosinophilia
179	11/12/23	Onchocerciasis
Duplicate	11/12/23	Loiasis
"	11/11/23	Myiasis
"	11/10/23	Rickettsia Pox
"	11/10/23	Endemic Typhus
"	11/10/23	Rocky Mountain Spotted Fever
"	11/10/23	Lyme Disease
"	11/10/23	St. Louis Encephalitis
"	11/09/23	Babesiosis
"	11/09/23	Powassan Encephalitis
"	11/09/23	West Nile Encephalitis
"	11/09/23	Japanese Virus Encephalitis
"	11/09/23	Chikungunya
178	11/08/23	Dengue

                                  Index I

Number	Date	Title
1	05/03/23	New brain cell formation after birth
2	04/29/23	Sugar and diabetes mellitus
3	04/10/13	Creatin / creatinine and kidney
4	04/15/23	Looking for essential amino acid
5	03/28/23	Cholesterol and lipoprotein
6	03/12/23	Anatomy of the human soul
7	03/08/23	C- Reactive protein
8	03/04/23	Liver cancer
9	02/26/23	Food poisoning
10	02/16/23	Peptic ulcer
11	02/02/23	Iron deficiency anemia
12	01/29/23	Cardiomegaly
13	01/21/23	Immune cells of the brain and spinal cord
14	01/17/23	Cornea and corneal transplant
15	01/12/23	Nasal septum
16	01/08/23	Eardrum
17	12/22/22	Neurotransmitter
18	12/14/22	Connective tissue and mixed connective tissue disease
19	12/21/22	Science of taste
20	12/03/22	Muscle disease
21	11/23/22	Cartilage and diseases of cartilage
22	11/19/22	Leishmaniasis
23	11/12/22	Malaria
24	11/03/22	Heat intolerance
25	11/04/22	How we see the outside world
26	10/31/22	Movement disorder
27	10/24/22	Epstein-Barr virus infection
28	10/23/22	Monkey pox
29	10/23/22	What Cerebellum does
30	10/18/22	Science of skin color
31	10/16/22	Speech disorder
32	10/13/22	Abnormal RBC morphology and significance
33	10/10/22	Eosinophils and diseases associated with eosinophils
34	10/03/22	Oral ulcer
35	10/01/22	Gut bacteria and human health
36	09/03/22	Long COVID
37	08/24/22	Bell's palsy
38	08/21/22	Dizziness and vertigo
39	07/24/22	Sudden death
40	06/15/22	Epilepsy
41	05/31/22	Regulation of body temperature
42	05/26/22	Oxygen radical
43	05/18/22	A Look at the diabetic kidney
44	04/29/22	Kidney and BP
45	04/16/22	Kidney stone
46	04/09/22	Chronic pancreatitis
47	04/03/22	Gene controlling human hair color
48	03/25/22	Red eye
49	03/21/22	Trace elements and human health
50	03/14/22	Penicillin allergy
51	03/10/22	Insulin resistance
52	03/19/22	Immune reaction
53	01/24/22	Interleukin-6
54	01/16/22	Lactic dehydrogenase
55	01/13/22	Pulmonary function test
56	01/10/22	Diabetes mellitus II and microvascular changes
57	12/30/21	Extragonadal germinal cell tumors
58	12/26/21	Hearing in old age
59	12/13/21	Dream
60	12/11/21	Memory
61	12/03/21	Sleep
62	12/03/21	Folic acid
63	11/30/21	Vitamin B12
64	11/19/21	Thalamus and outline of the sensory system
65	11/19/21	Adrenal glands
66	10/09/21	Mycoplasma pneumonia
67	10/02/21	Respiratory failure - pathophysiology
68	09/29/21	Near drowning
69	09/23/21	Spit /Sputum / Phlegm
70	09/19/21	Noncardiac pulmonary edema
71	09/10/21	Eosinophil and eosinophilic pneumonia
72	09/03/21	Pulmonary arterial hypertension
73	08/01/21	Pleural effusion
74	08/30/21	Multiple myeloma
75	08/20/21	Pituitary gland
76	08/18/21	Appendix
77	08/17/21	Color of urine
78	08/15/21	Sarcoidosis
79	08/14/21	Thymus
80	08/13/21	Liver
81	08/11/21	Pancreas
82	07/11/21	Bronchogenic cyst
83	07/19/21	Speech disorder
84	07/11/21	Stunned myocardium
85	07/08/21	Slow growing cancer of the lungs
86	07/06/21	Benign tumors of the lungs
87	07/03/21	Fever
88	07/01/21	Common cold
89	06/28/21	Sternutation
90	06/28/21	Cough
91	06/26/21	I can't breathe
92	06/24/21	Chest pain
93	06/22/21	Single pulmonary nodule
94	06/21/21	Psoriasis
95	03/07/21	Lung abscess
96	03/07/21	Empyema
97	03/04/21	Science of high altitude pulmonary edema
98	02/28/21	Non-alcoholic fatty liver disease
99	02/21/21	Embolus
100	02/15/21	A-V malformation
101	02/11/21	6 minute walk test
102	02/09/21	Hemoptysis
103	02/07/21	Bronchiectasis
104	02/03/21	Understanding chronic bronchitis
105	01/28/21	Mycobacteria avium intercellulare
106	01/28/21	Mycobacterium kansasii infection
107	01/24/21	Clinical presentation of pulmonary tuberculosis
108	01/20/21	Metal fumes and lung disease
109	01/09/21	Black lung disease
110	01/14/21	Hypersensitive pneumonitis
111	01/14/21	Radiation pneumonitis
112	01/09/21	Hyperbaric oxygen therapy
113	01/09/21	Aspergillus and asthma
114	01/04/21	Cystic fibrosis and Pseudomonas
115	01/01/21	Migratory pneumonia
116	12/31/20	CAP and walking pneumonia
117	12/30/20	Legionaries' disease
118	12/29/20	Surfactant and alveolar proteinosis
119	12/27/20	IgA and IgA associated diseases
120	12/26/20	Hemoglobin and Bets Thalassemia
121	10/18/20	Iron and Hemochromatosis
122	10/12/20	Fighting with a killer
123	10/11/20	Mutation of a gene of Psoriasis
124	09/01/20	Idiopathic pulmonary fibrosis
125	08/25/20	Memory and dementia
126	08/19/20	Amyloidosis
127	08/15/20	Leukotrienes
128	08/14/20	Prostaglandins
129	08/11/20	Controlling malaria
130	08/06/20	Advances in the treatment of Parkinson's disease
131	08/02/20	Diagnosis of pulmonary tuberculosis
132	07/27/20	Interleukin
133	06/01/20	Platelets
134	05/30/20	Oral agents of DM2
135	05/26/20	Immunocytes and Immunomodulators
136	05/15/20	Stem cells and stem cell transplantation
137	05/05/20	COVID-19 vaccine
138	03/09/20	Ewing's sarcoma
139	05/27/19	A miserable human malady
140	05/09/19	Multiple Sclerosis
141	05/01/19	The soft bones and porous bones
142	04/20/19	Blood thinners
143	04/13/19	Enlarged prostate gland
144	04/11/19	Chronic Myeloid leukemia
145	04/07/19	The other side of the transplant
146	03/30/19	Human Heart
147	07/01/17	The spleen
148	07/09/11	The abnormal gene and cancer
149	07/02/11	Fat cell - Adipocytes
150	06/13/11	Carcinoid and other neuroendocrine tumors
151	05/30/11	Parathyroid glands and Parathyroid hormone
152	03/29/11	Emphysema
153	03/22/11	Phosphorus
154	03/07/11	Calcium
155	03/03/11	Vitamin D
156	01/31/11	Hunger and obesity
157	01/20/11	Hepatitis
158	01/17/11	Wheezing
159	01/06/11	Sinister headache
160	10/10/11	Varicose veins
161	05/14/09	Double vision
162	05/06/09	A sluggish Thyroid gland
163	05/01/09	Human Hair
164	04/2720/09	Blood sugar
165	04/23/2009	Calcium and bone
166	04/2420/09	Know your Blood Pressure
167	11/04/2009	Lock at your hand
168	11/12/2023	Onchocerciasis
169	11/12/2023	Loiasis
170	11/11/2023	Myiasis
171	11/10/2023	Rickettsia pox
172	11/10/2023	Epidemic Typhus
173	11102023	Rocky Mountain Spotted Fever
175	11/10/2023	St. Louis Encephalitis
176	11/09/2023	Babesiosis
177	11/09/2023	Powassan Encephalitis

New Brain Cell Formation After Birth

                                              Brain Cell Growth After Birth.

                                             PKGhatak, MD

The study of Postnatal Neurogenesis of the brain, meaning brain cell growth after birth,  has become an urgent issue in order to find a cure for Alzheimer's disease and Parkinson's disease.

The word “growth” includes new neuron formation and growth of the size of individual nerve cells. In the brain, nerve cells are mainly of three kinds - 1. Neurons, 2. Supporting cells called Microglia and 3. Limited numbers of Ependymal cells which secrete the cerebrospinal fluid. Nerve fibers - axons and dendrons proliferate beyond comprehension. The growth of the brain after birth encompasses all these components. But scientists are mainly interested in New Neuron Formation.

Few eye-opening numbers about the brain:

By the time of birth, the newborn brain has 100 billion neurons and 100 trillion synapses. To meet that goal, the developing brain generated about a quarter million cells per minute.  Though smaller in size, the child's brain makes 50 % more synaptic connections along with the growth of nerve fibers. By the age of 8, the brain of a child has achieved near complete growth and development. Thereafter, remodeling of the brain takes place, which is primarily of pruning of synapses; migration of neurons and new neuron formations take place in the Hippocampus, Cerebellum and Prefrontal Cortex of the brain.

Stages of growth:

There are several stages of growth and development. They are - Neuron generation, Differentiation, Neuron Migration, Synaptogenesis, Myelination and Synapse Pruning.

                This article is a brief discussion of new neuron formation.

Studies are performed in the laboratory on small mammals like rats. Then those experiments that do not require invasive procedures are carried out on humans. 

                                                           Memory.

Memory acquisition in children grows in geometric proportion and then continues at a much slower pace throughout the entire adult life. Research is going on to verify whether new information stored as memory requires new neuron generation. Hippocampus, which is the site of memory formation and short time storage site, is the main area of interest for the researchers.

New nerve cells grow from Neuronal Stem Cell:

 In the subgranular layer of the Dentate Gyrus close to the hilum, the Neuronal Stem Cells are present. The stem cells divide and increase in numbers and form new neurons. The newly formed neurons migrate to the granular layer of the DN and then migrate to the hippocampus. Neurons produce new synapses very rapidly in 5 stages, including the capacity to generate calbindin, a marker for synaptic integration.

Factors influencing Neuron formation:

Stress, glucocorticoids, depression and chronic illness delay or suppress new neuron formation and synaptic connections and in fact, may even prune the already existing synapses.

Enhancement of neurogenesis is seen by the action of brain-derived neurotrophic factor (BDNF), fibroblast growth factor (FGF), serotonin and those drugs that block the reuptake of serotonin, such as Fluoxetine. Metformin also increases neurogenesis in cell cultures containing human neuronal stem cells and in animal models.

The question is whether these experimental successes can be duplicated in patients suffering from Alzheimer's disease, Parkinson's disease, ALS and Huntington’s disease.

**************************************

Sugar and Diabetes mellitus

 11 Draft.

                                             Sugar and Diabetes mellitus.

                                              PKGhatak, MD

Sugar belongs to carbohydrates and is essential for humans. Sugar is classified as a monosaccharide and a disaccharide. Monosaccharides are Glucose, Fructose and Galactose. Disaccharides are composed of two molecules of monosaccharides and are Sucrose, Maltose and Lactose. When disaccharides break down in the gastrointestinal tract by specific enzymes, they yield the following monosaccharides.

Sucrose = Glucose + Fructose.

Maltose = Glucose + Glucose

Lactose = Glucose + Galacose.

All monosaccharides are six-carbon compounds. Fructose is the sugar of fruits and vegetables. The common source of fructose is cane sugar, table sugar, beet sugar, and soft drinks. Milk and milk products contain lactose. Maltose is a man-made disaccharide, obtained mostly from barley grain.

Glucose and fructose resemble each other both chemically; the only difference is that glucose is an aldehyde and fructose a ketone. Maltose is also an aldehyde like glucose and maltose is an Epimer of C-4 glucose. Epimer differs only in the position of the OH group of one C atom. All three monosaccharides are present as Isoforms (L & D isomers).

Carbohydrate metabolism:

The energy required for sustaining life comes from ingested carbohydrates, fat and proteins.

The breakdown of complex carbohydrates ( Cellulose, starch, and dextran) starts in the mouth by the enzyme - salivary amylase. The breakdown of carbohydrates continues in the intestine by the pancreatic amylase and various other enzymes, including Lactase, which splits Lactose into glucose and galactose. Many adults have Lactose intolerance due to either acquired lactase deficiency or congenital deficiency of lactase.

Glucose, fructose and galactose, once formed inside the lumen of the small intestine, follow their own path of metabolism. There is similarity and also a different paths of the three sugars.

                                 Glucose.

Glucose is ferried across the gut lumen into the intestinal enterocytes by the Sodium/glucose co-transporter 1 (SGLT1). SGLT1 is a member of the solute carrier family SLC 5 transporter. SGLT1 also selectively reabsorbs glucose completely from the glomerular filtrate in the proximal tubule, unless the amount of glucose in the filtrate exceeds the maximum reabsorptive capacity of SGLT, as that happens in diabetes mellitus.

Glucose utilization.

In the liver, glucose is converted into glycogen.

Glucose is taken up by all living cells by the action of Insulin. Insulin fuses with the cell membrane and creates an opening for glucose molecules to enter the cell cytoplasm and then glucose molecules are taken up by the mitochondria. Glucose is used up in the tricarboxylic cycle and produces energy, generates ATPs and the end products are CO2 and H2O.

In the muscles: Some glucose is reserved in the muscles as glycogen for future use. Most of the glucose is utilized as fuel.

Hexose monophosphate shunt (HMS):

HMS is also known by other names like pentose phosphate pathways. It takes two separate paths -

1. Aerobic. This path leads to the generation of energy and NADPH (nicotinamide adenine dinucleotide phosphate). NADPH is required for the biosynthesis of fatty acids, cholesterol, and neurotransmitters.

2. Anaerobic. This path leads to the production of pentose sugars. Pentose sugars are components of Nucleic acids and nucleotides. Also through the anaerobic path, Erytrose 4 phosphate is produced. Erytrose 4 phosphate is a component of aromatic amino acids.

                                      Fructose:

Important dietary sources of fructose are fruits, honey, high-fructose corn syrup (soft drinks), and table sugar (sucrose). The enzyme, Sucrase, breaks sucrose into glucose and fructose in the intestine.

Absorption.

GLT transporter is used for fructose absorption from the gut lumen by GLT 2 and from the enterocytes to the portal vein by GLT 5 transporter. There is no fructose in the peripheral blood or in the glomerular filtrate

Fructose utilization.

Fructose is taken up mainly by the liver and only a limited amount by the kidneys, adipose tissues, and muscles. In the liver, fructose is converted into glycogen and all excess fructose is used in the synthesis of Triglyceride. The majority of body cells are unable to utilize fructose directly, and all the reactions involved in fructose metabolism take place outside the mitochondria. And that too is limited to the liver, adipose tissue, gut and testes.

There are two paths for Fructose utilization:

Hexokinase.

In the muscles and fatty tissue, fructose is phosphorylated by fructose-6 phosphatase and then enters the glycolysis via the tricarboxylic acid cycle. Insulin is not required for fructose metabolism. The majority of cells are not able to metabolize fructose.

In the Liver:

The liver turns fructose to triglyceride and triglyceride is stored in the liver cells as fat. When excess fat accumulates in hepatocytes it causes non-alcoholic fatty liver disease. The liver delivers triglyceride to fat cells of the body and an excess amount of fatty tissue produces obesity.

Relation between Fructose and insulin.

Fructose does not stimulate Insulin secretion. Glucose on the other hand stimulates insulin secretion. Insulin, when it reaches the Hypothalamus, releases the Leptin hormone. Leptin suppresses hunger. Increasing fructose in the diet has no effect on hunger suppression and contributes to obesity.

The adverse effects of high triglyceride in the genesis of atherosclerosis and coronary artery disease are dealt with elsewhere in Humihealth. blogspot.com.

                                           Galactose:

Milk sugar is lactose. In newborns and young children, lactose supplies the majority of energy requirements. Lactase splits lactose into glucose and galactose. SGLT 1 transports galactose, like glucose, from the gut lumen to endothelial cells. Galactose along with glucose is taken up by the liver. Galactose is entirely utilized in the liver for the conversion into glucose by multiple enzymatic steps involving specific enzymes for those reactions. Intermediate compounds are galactose 1 phosphate and Uridine diphosphate glucose (UDP-glucose). The further enzymatic reaction produces UDP-galactose and glucose 1-phosphate and by epimerization forms UDP-glucose. Several other downstream metabolic paths are involved in galactose metabolism to produce other compounds.

Synthesis of Galactose and Lactose by lactating women.

The milk glands of the breast synthesize galactose from the 3-carbon Glycerol, an intermediate product of glucose utilization. The formation of lactose takes place within the gland by the reverse action of the enzyme lactase, and the glucose molecules are obtained from the blood.

                                 Blood sugar:

Blood sugar is Glucose, and glucose only.

It is customary to obtain blood chemistry at the annual physical examination for all adults and children in the USA. One of the routine tests is fasting blood sugar(FBS). If the FBS is 100 mg/dL or over, the result would be marked as abnormal. Based on the actual FBS, the attending physician informs the patient of the possibility of a prediabetic condition or diabetes mellitus.

FBS:

Although a fasting state is not difficult to understand and adhere to, it has many variables which may significantly alter the FBS results. When such a situation arises, the test is repeated under proper overnight fasting. That too is variable and controversial. Even then FBS is good only for that moment because blood glucose level varies from hour to hour based on food intake and physical activities.  Instant blood glucose is essential for the determination of insulin dose. But glucose levels for the long term determine the long-term prognosis of diabetes mellitus. This led to the introduction of the Hemoglobin A1C blood test (HbA1C).

                                    HbA1C test:

The reaction of Glucose with Hemoglobin:

The beta chain of the hemoglobin molecule has a terminal valine residue. Glucose molecules irreversibly bind with valine. The saturation of this N-terminal of valine with glucose is proportional to the average blood glucose level. Hemoglobin A1C is the percentage of glycated hemoglobin. Because the life of a RBC is about 120 days, the HbA1C is the sum of old RBCs and newly formed RBCs; the older RBCs have more time to combine with glucose whereas new RBCs hardly have time to be glycated. And HbC1 is a measure of the average blood glucose over 90 to 120 days. HbA1C is remarkably stable and reproducible in an individual.

False high HbA1C may result from excess hemoglobin, dehydration,  frequent blood transfusion, splenectomy, or polycythemia. A low HbA1C is due to low hemoglobin level which may result from iron deficiency anemia, beta thalassemia (absent beta chain of hemoglobin), hemolytic anemia, etc

The glycation of hemoglobin involves two stages. The initial reaction is the chemical binding, then the non-enzymatic rearrangement of the molecule to a stable ketamine ( keto-amine).

                 Classification of Diabetes and Diagnostic Tests:

Diabetes mellitus is a distinct entity, only the common link is elevated blood glucose levels.

Type I diabetes is due to a complete lack of insulin production from the beta cells of the pancreas. The onset of the disease is early, usually in teens and generally sudden, caused usually by a viral infection. Ketoacidosis and weight loss and debility are hallmarks of diabetes type I.

Type II diabetes is generally detected in middle age. It has an insidious onset and progresses slowly but steadily and produces microvascular changes in the retina, kidneys, brain and peripheral arteries. DM type II runs in the family. The blood level of insulin is usually high and insulin resistance in the tissue or structural abnormality of insulin is often demonstrated. Autoimmune diseases can manifest as diabetes by producing antibodies to insulin.

A group of diseases associated with high blood glucose levels due to various reasons other than lack of insulin or structurally abnormal insulin. These entities are Cushing's disease, chronic use of cortisone and other steroid products, pancreatitis, carcinoma of the pancreas, Liver disease, Cystic fibrosis, Polycystic disease of the ovary, stress, trauma and following severe burns, chronic use of epinephrine, use of Cyclosporine and Tacrolimus, hyperalimentation, obesity, pregnancy, poor diet habits, sedentary lifestyle and lack of physical activities.

People with high blood glucose are prone to infection, but non-diabetes hyperglycemic patients do not develop ketoacidosis or progressive microvascular change unless they are prediabetic, to begin with.

                              Pregnancy and Blood Glucose:

Pregnancy is a risk factor for the development of Diabetes mellitus (DM). To identify the pregnant individual at risk of DM, an Oral Glucose Tolerance Test (OGTT) is performed at 24 to 28 weeks of pregnancy on a routine basis.

OGTT:

One step OGTT. A fasting blood glucose is drawn. A concentrated glucose solution of 50 gm of glucose dissolved in 250 ml of water is ingested. The patient is asked to remain sitting or remain inactive during the test. Blood samples are collected at 60 and 120 mins following ingestion of glucose.

In a modified OGTT, the patient has been coached adequately, and fingertip blood sugar test kits and other supplies are given to the patient and asked to do the test at home; then mail back the blood samples by post.

In multi-step OGTT, in selected patients, the test period is 3 hrs. long and blood samples are collected at 30, 50, 90, 120. 150 and 180 minutes following oral glucose ingestion.

OGTT test is also done in very few selected Non-DM patients with an oral dose of glucose 1.75 gm / Kg body weight. Blood samples are taken at 60, 120 and 180 mins. The 3-hour OGTT is done where delayed gastric emptying or delayed pancreatic reactions to a glucose load are suspected.

Interpretation of OGTT.

Diagnostic Criteria of	Fasting Glucose in mg/dL	60 minutes post glucose dose in mg/dL	120 minutes post glucose dose in mg/dL
Normal Gestational	Less than 90	130 to 140	Less than 120
Gestational DM	Greater than 95	Greater than 140	Greater than 120
Normal Nonpregnant	60 to 100	Less than 200	Less than 140
Impaired Nonpregnant	100 to 125		140 to 200
DM nonpregnant	100 to 126		More than 200

Diagnostic Tests for Diabetes Mellitus:

Diabetes Type I.

In an infant, child, or teenager, low or high blood glucose should not be dismissed. A proper evaluation requires a repeat FBS or an OGT Test in selected cases. Blood insulin level is a preferred test when a young individual develops ketoacidosis or unusual loss of weight and exhibits low energy levels.

Diabetes Type II.

For adults suspected of having DM, an 8-hour fasting glucose is the initial test. If FBS is above 100 mg/dL, then the next test is the HbA1C test. Fasting is not necessary for the HbA1C test.

HbA1C criteria for normal, prediabetes and DM are as follows:

Normal or negative for DM –> HbA1c is 5.5 or less.

Prediabetic –> HbA1C is between 5.6 to 6.9

Diabetes mellitus-> HbA1C is 7 or over 7.

Care should be taken if patients have hemoglobinopathy or any red cell abnormalities. Iron deficiency anemia gives false lower values of HbA1C.

2-hour postprandial blood sugar, usually known as 2hr PP sugar, is a relic of the past and has no clinical importance in the present-day management of DM. A random sugar test is preferable instead.

Interpretation of Random blood glucose test.

Normal- Glucose less than 140 mg/dL or HbA1C 4.6% or less.

Prediabetic- Glucose between 140 to 200 mg /dL or HbA1C 4.7 % to 6.4 %

Diabetic – Glucose over 200mg /dL or HbA1C over 6.5 %

After the initial diagnosis of DM is made, further tests can be done on an individual. Some of these tests are - the blood level of insulin, insulin antibodies, abnormal structure of circulating insulin, the status of the beta cells of the pancreas, liver function tests, blood level of glucagon, pituitary growth hormones, steroid hormones, etc. In DM type II, a family history of DM usually is very strong.

 [  The formula for conversion of HbA1C into Glucose in mg/dL.

( 28.7 x HbA1C ) - 46.7 = Glucose in mg/dL.

Formula to covert plasma glucose in mg/dL to mmol/L

Glucose in mg / 18. =  mmol/L  ]

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Creatine / Creatinine and Kidney

                                            Creatine / Creatinine and Kidney

                                               PKGhatak, MD

Creatine is an amino acid, chemically it is methylguanidoacetic acid. Creatine is mostly present in skeletal and heart muscles and in small quantities in the brain and testes.

Creatine

Creatinine is the metabolic end product of creatine. Creatinine is formed in the muscles from anhydrous creatine by a non-enzymatic removal of H20 and intramolecular cyclization. 

Creatinine

Blood levels of Creatinine - for men 0.75 to 1.5 mg/dL or 65 to 119 micromoles/L/L and for adult women -0.6 to 1.04 mg/dL or 52 to 92 micromoles/L.

The creation comes from two sources. A. Biosynthesis. B. Form diet.

A. Biosynthesis:

It takes place in two stages and in two places. The kidneys are the main place of biosynthesis in the first stage. However, when both kidneys are removed, about 15 % of the biosynthesis of creatine takes place in the pancreas.

The enzyme L-Arginine-Glycine-amidinotransferase catalyzes Glycine + Arginine to form Guadinoacetetic acid and Ornithine. Guadinoacetic acid, known as Glycocyamine and is transported by a carrier protein to the liver.

Control of biosynthesis.

GI source of creatine has a negative feedback effect on the renal enzyme guanidinoacetate. When GI absorption is high, renal production of guanidinoacetate is reduced proportionally but this has no effect on the production of creatine in the liver. However, creatine synthesis in the liver is dependent on kidney transamidase activity and hepatic synthesis is reduced as less glycocyamine is available in the liver.

Hormone influence.

Hyperthyroidism slows kidney transamidase activity due to high blood creatine levels.

Genetic mutation:

Mutation of the gene causing transamidase deficiency, an inborn error of creatine synthesis, is characterized by language, cognitive and behavior disorders.

B. In the liver Guadinoacetetic acid reacts with S-adenosylmethionine by enzyme methyltransferase and from Creatine and Adenosylhomocysteine. Methionine is the principal methyl donor; other minor methyl donors are choline and betaine. This reaction is not reversible. Glutathione and other reducing substances are required for the optimal activity of this enzyme.

B. Dietary source of creatine.

Food rich in guadiniacetic acid (GAA) is meat, poultry, fish, milk and milk products, and apple and loquat. Of the total turnover of 2 gm per day, a normal diet supplies only 5 % of GAA. The rest comes from biosynthesis.

Creatine in the muscles:

Creatine is transported to muscles and upon entering the muscle cells, creatine is acted upon by ATP ( adenosine triphosphate) to turn it into Creatine phosphate by ATP-creatine-phosphorylase enzyme. Creatine phosphate becomes cell bound and can not escape the cell. It is a high energy molecule, that easily transfers high energy phosphate to ADP when the muscle is contracting rapidly and exhausts all ATP. Conversion of ADP to ATP is catalyzed by adenyl kinase. Lactate and acetate block this reaction when these organic acids accumulate in muscles during prolonged activities. In the heart, the myocardium is capable of sustaining activities by utilizing fatty acids. lactate and ketone as fuels.

In the resting stage, muscle contains 6 times as much creatine-phosphate as ATP. Creatine phosphate is proportional to the body's muscle mass. In the muscles, 85 % of creatine is present as creatine phosphate. And all the creatine produced by the muscles is excreted in the urine. And the 24-hour urinary creatinine is remarkably constant in an individual.

Interest in improving muscular performance by creatine.

Sports :

Athletic performance is enhanced by a higher concentration of creatine-phosphate in the muscles and creatine is used as a nutritional supplement to that effect. Creatine supplement is available as creatine citrate, creatine monohydrate and creatine pyruvate.

Experimental use of creatine in diseases:

In ALS, Muscular dystrophy,  and Multiple sclerosis, creatine supplements are used but no significant improvement is noticeable.

Creatine ethyl ester(CEE):

A new form of creatine supplement, creatine ethyl ester, is available. It has an advantage over other forms because it resists degradation in the stomach and bioavailability is greater. It is soluble in fat and has much higher membrane permeability. It is slowly metabolized and so muscle performance can have a quicker onset and be more sustained at a high level of performance.

The half-life of creatine is 3 hrs. 3 to 6 hourly dosing is necessary in order to maintain high muscle creatine concentration. Once the supplement is stopped, the muscle creatine returns to baseline in 4 weeks.

Renal Excretion of Creatinine.

Creatinine in the blood is derived as the end product of creatine phosphate metabolism in the muscles. Creatinine is water soluble and readily filtered by the glomeruli of the kidney; about 15 % of creatinine is secreted by the cells of the proximal renal tubules in healthy adults. In renal failure, the tubular secretion may increase to 30 %, and some creatinine loss takes place through the intestine.

Effect of high protein diet.

A normal diet contains creatinine of about 1/10^th of the daily requirement of creatine. When placed on a high protein diet, the fecal loss of creatinine rises sharply and creatinine only minimally.

Serum creatinine and creatinine clearance capacity of the kidney:

The Glomerular Filtration Rate (GFR) of Creatinine is considered the standard test of renal filtration capacity in health and in diseases. Any reduction in GFR is an indication of renal disease.

To detect the true glomerular filtration capacity, the test material must only be filtered by the kidney and should not be secreted either by renal tubules or the intestine. Creatinine is not ideal from that point because it is also lost in other ways as stated above.

Such an agent was Inulin. Inulin is a complex carbohydrate, obtained from the roots of the Chicory plant. In earlier times, Inulin clearance was the gold standard for renal filtration. It is now abandoned because of multiple factors including the very high cost of conducting tests requiring a hospital stay.

Then several radioactive agents were introduced. These tests were also given up due to concerns about radiation exposure to patients and clinic personnel.

Creatinine Clearance Test (CCT) is now accepted as GFR in health and in renal diseases.

Modified creatinine clearance test.

A standard CCT requires the meticulous collection of 24 hrs.' urine and several blood creatinine level determinations.

Soon a simpler test came into medical practice, which is equal to the standard CCT in every respect if not better. The modified CTT is done by deduction. The GFR is determined from one serum creatinine level.

The formula of GFR is -

For adult males:

GFR = 141 x (Scr/79.6) – 0.41 x (0.993)Age.

For adult females:

GFR = 144 x (Scr/61.9) – 1.209 x ( 0.993)Age.

Scr = serum creatinine in micromoles per liter.

[ Conversion table- mg/dL to micromoles/L of creatinine.

1mg /dL of creatinine = 0.01131222 micromoles /L.]

Correction factors are available for non-white races.

Normal GFR is above 60 ml/min and usually 80 to 160 ml/min

Other formulas:

CKG -EPI Creatinine Equation 2021.

eGFR =

142* min(standardized Scr/K, 1)α * max(standardized Scr/K, 1)-1.200 * 0.9938Age * 1.012 [if female]

eGFR (estimated glomerular filtration rate) = mL/min/ 1.73 m2 ( m 2 = square meter)

Scr (serum creatinine) = mg/dL

K = 0.7 (females) or 0.9 (males)

α = -0.241 (females) or -0.302 (males)

min = indicates the minimum of Scr/K or 1

max = indicates the maximum of Scr/K or 1.

Calculate serum creatinine from GFR

eGFR= mL/min/1.73m 2 ( m 2 = square meter)

Serum Creatinine * µmol/L.

The typical range for serum creatinine is: For adult men, 0.74 to 1.35 mg/dL (65.4 to 119.3 micromoles/L) For adult women, 0.59 to 1.04 mg/dL (52.2 to 91.9 micromoles/L).

Latest method.

An iodinated compound, Iohexol, is a safe contrast agent used in radiological studies. Iohexol is now used for GFR determination. Iohexol does not combine with blood proteins and is well distributed in the body. It is excreted by glomerular filtration only. No other renal or GI process is involved in the excretion of Iohexol.

After giving a loading dose by IV at the clinic, the subject/patient is sent home to collect blood samples on supplied papers from fingertip puncture,( very much like the Glucose home test) at certain intervals. And when the test is completed, dried blood samples on paper are mailed back in a prepaid envelope. The Iohexol concentration in the dried blood samples is determined by Liquid Chromatography. And the GFR is calculated by a given formula. Recently, the  American Diabetes Association recommended the Iohexol GFR test on an annual basis in diabetics. This test is called Dried Blood Spot (DBS) for GFR.

Stress Tests for Kidneys.

Like cardiac stress tests, Kidney Stress Tests are possible. Kidney stress tests are generally not done in clinical practice but are important for drug manufacturers and researchers.

These are some of the kidney stress tests.

1. High protein diet test. To test the GFR. 2. Creatinine load test. To test the proximal tubular cation transfer ability. 3. Water restriction test. To test the kidney's ability to concentrate urine in the collecting tubules. 4. Ammonium chloride loading test. To study H ion retention ability. 5. Oral bicarbonate load test. To study H ion handling capacity.

If one is due for a blood test, which includes serum creatinine, on making a request for a copy of test results at the time of registration, the lab will test the results. On a closer look, one will find an estimated GFR at the bottom. If GFR is a bit low, no need to be disheartened. The lab might have given the results based on a formula that takes the Body Surface Area into account. And sure enough, the lab did not take height and weight. So recalculating the result with actual height and weight might give a better GFR number.

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Looking for Essentials Amino Acids.

                                  Searching for Essential Amino Acids.

                                     PKGhatak, MD

Essential amino acids for humans are 9 in number, namely: Histidine, Isoleucine, Leucine, Lysine, Methionine. Phenylalanine, Threonine, Tryptophan and Valine. Essential amino acids must be supplied in the food because our body can not synthesize them from other sources. Our body, however, can synthesize these non–essential amino acids, and common among them are Glycine, Alanine, Serine, Cysteine, Arginine, Aspartic acid, Glutamic acid, Arginine, Lysine, Tyrosine, Proline and Homocysteine. Amino acids are the main building blocks of protein molecules.

The human body is composed of 62 % water, 16% fat, 16 % proteins, 6 % minerals, 1 % carbohydrates and traces of vitamins and trace elements.

The function of Amino acids.

Both essential and nonessential amino acids are constituents of every cell and tissue of our body- from hair to the bone marrow cells and in between everything else. In addition, amino acids are required for growth, tissue repairs, immunity, hormone production and metabolic functions.

A few specific functions of individual amino acids are highlighted in the following paragraph.

Histidine - Blood cell formation.

Isoleucine - Increases growth hormone production. Skin and bone repairs.

Lysine - Calcium absorption, Collagen formation of tendons, cartilages, and skin.

Methionine - Antioxidant. Detoxify heavy metals.

Phenylalanine – Formation of the neurotransmitter, calcitonin and melanin.  and also the source of Tyrosine.

Threonine - Formation of elastin, the enamel of the tooth and mucin production from glands. Glucose metabolism.

Tryptophan - Formation of serotonin and melatonin, DNA repairs, Niacin    ( vitamin B3).

Valine – Muscle growth and health.

Are humans omnivorous.

No other living organism exists today that comes close to humans in choosing what to eat—from insects to the most poisonous puffer fish and snakes.

According to the WHO in the year 2021, a family of four in the USA consumed. 800 lbs of meat per month. 70 lbs of chicken per person per month was eaten during that time.

350 million tons of meat were consumed globally every year, of which pork was number one. China produced and consumed the most pork, and the USA came in third place. The USA is the largest consumer of beef and India came in 5th place; that must surprise some people. Fish consumption is highest per capita in Iceland, at about 200 lbs per year, the USA came 11th place by using 50 lbs per capita and still managed the second place by eating 290 eggs per person, only Japan consumed more, about 320 eggs per person.

The current trend in the USA.

In recent years, a vegetarian diet has gained popularity among the health and environment-conscious sections of the wealthier nations. Various degrees of vegetarianism exist. True vegetarians or vegans do not eat any meat or fish and avoid eggs or milk altogether. In India, where a major section of the population has been vegetarian for centuries, however, they consume milk from the cow, buffalo, goat and a few isolated tribes drink milk from camels. Some other Indians consider themselves vegetarian, but eat eggs and some also eat fish,  but not any animal meat.

Whatever form of vegetarian one may be, the main source of protein in their diet comes from plants. And most green parts of plants are not rich in proteins, the seeds of plants are. To meet the demands of plant seeds that are rich in proteins, more selective cultivation is required. It is becoming an important agricultural consideration for meeting this growing demand but must be met in sustainable and environmentally protective ways.

Protein requirement.

A growing child in utero needs 925 grams of protein and the mother supplies that amount during pregnancy. During lactation, an additional 1.3 grams of proteins per 100 ml of milk is needed.

Adults require 0.8 grams/Kg body weight ( stand height/weight). The elderly actually need less but defects in digestion and absorption are considered and the recommendation is like an adult - 0.8 g/Kg.

Obligatory Nitrogen Loss.

Protein turnover in the body is a continuous process of synthesis, breakdown and elimination of toxic nitrogenous waste products. When placed in a protein free but calorie sufficient diet, the body extracts the essential amino acids by breaking down proteins. This system is very efficient but the nitrogenous portion that is eliminated in urine and stool must be supplied in the food.

Effects of protein starvation.

Pictures of emaciated people ravaged by wars or severe famine need no further explanation. A short stature of a growing child, thin limbs, a pot belly, edema, fragile skin and orange hairs are the results of protein deficiency. Blood levels of albumin and hormones are low in these children. In nephrotic syndrome and severe liver cirrhosis, frequent infections and various complications are the results of derailed protein metabolic machinery of the body. Specific amino acid deficiency can occur due to inherited metabolic defects and the consequences of those can be found elsewhere.

Plant Proteins.

Many plant proteins are not available to humans due to the complex nature of the molecules, which are not easily digested or absorbed in the gut. Some plant proteins are poisonous, like in cassava.

Good source of vegetable proteins.

The high plant protein content is given here in descending order. It is the total amount of available protein but not in terms of essential amino content. The list of plant sources of proteins: Durham wheat, cashew nuts, quinoa seeds and ancient grains, dried seaweeds, rice, pumpkin seeds, beans, peas and raw soya beans.

Some individual plants with some good sources of essential amino acids are listed as -

Durham wheat supplies a fair amount of histidine, phenylalanine, tryptophan, valine and threonine.

Cashew nuts are a good source of phenylalanine, valine, leucine, lysine, Isoleucine and methionine.

Pumpkin seeds supply phenylalanine, tryptophan, Isoleucine, leucine and threonine.

Quinoa and ancient grains. Quinoa contains all 9 essential amino acids. Several other ancient grains are also good sources of proteins, chief among them are barley, farrow, buckwheat, millet, sorghum, kamut and teff. Each one has many other health benefits. Quinoa is an annual herb that belongs to the Chenopodium family. The grain contains 8 grams of protein per cup of cooked grain and is highly sought after because it supplies all nine essential amino acids. The protein of quinoa is 11s-globulin and contains no gluten. In addition, quinoa supplies unsaturated fatty acids, flavonoids, vitamins and minerals.

The rest of this group of grains contain more or less the same amount of proteins and are good sources of essential amino acids, but the amount varies from one to the other. All are good sources of micronutrients and antioxidants.

Soya beans have a good amount of leucine, lysine and phenylalanine.

Seaweeds are rich in histidine, leucine and lysine.

Peas and beans also supply fair amounts of phenylalanine, valine and threonine.

The world is always changing, and the rate of change has accelerated greatly in the last two or three centuries. The younger people of the present generation are much more concerned with animal sources of protein food along with other climate concerns. Eating proteins from nonanimal sources has come to attention lately from the processed food industries. This may be good or bad, only the future will tell.

Observing the effects of mass tourism causing accelerated degradation of the environment, like what has been done to Vienna and the Galapagos islands, should ring an alarm bell about this mass movement. No one can predict what that would do to the forested land in order to meet the demand for plant protein for human consumption.

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